E-mail: secretary@worldpharmaconference.com | USA : +1-646-828-7579, UK : +44-203-695-1242 | November 16-18, 2017, Barcelona, Spain  

SCIENTIFIC PROGRAM

Keynote Speaker

Joël Richard
IPSEN
France

Title: Delivery of Peptides by Non-Invasive Routes: Focus on Successful Oral Technologies Progressing in the Clinic and Future Challenges

Biography: Dr Joël Richard is currently Senior Vice President, Peptides in IPSEN (France). He is globally leading all the pharmaceutical development activities of peptide-based products, including APIs and drug products, with major franchises in Oncology, Endocrinology and Neurology. Dr Richard has more than 25 years of experience in chemistry and biopharmaceutical R&D, including several global senior positions in various Biotech and Pharma companies (Ipsen, Merck, Serono, …) . Since 1996, Dr Richard has focused his research activity on innovative formulation technologies and drug delivery systems (such as microspheres, nanoparticles, nanocapsules, chemically-modified proteins, supercritical fluid technology . . .), especially for injectable peptide and protein formulations. Dr Richard graduated from Ecole NormaleSupérieure (Cachan, 1985) and has got a PhD in Materials Science (University of Paris VI, 1987). He has published 67 peer-reviewed scientific papers, 8 book chapters and 2 review editorials in various fields (polymers, colloids and interfaces, drug delivery, supercritical fluids, protein formulations, nanoparticles, sustained-release formulations . . .). He is the author of more than 120 international communications and 53 patent families.

Abstract: Due to their physicochemical characteristics, peptides are usually administered through the parenteral route, often several times daily. Injectable sustained-release peptide formulations based on biodegradable microparticles or implants have been very successful to enhance patient adherence and convenience, and increase safety and efficacy [1]. They are likely to remain a significant and important part of the new peptide products coming to the market. However, the tremendous developments in alternative non-invasive routes of delivery are likely to result in more and more peptides being delivered by the transdermal, nasal, inhalation and oral routes [2]. The main purpose of this talk will be to analyze and compare the various alternative non-invasive peptide delivery technologies progressing in the clinic, discussing the pros and cons of these technologies in regards to stability, bioavailability, safety/efficacy balance, impact on costs of goods and manufacturability [3]. A special emphasis will be put on oral peptide technologies progressing successfully in the clinic, the key learnings from ongoing clinical studies and the future challenges anticipated for filing and launching oral peptide products in the next years.


Keynote Speaker

Celine Cano
Newcastle University
UK

Title: Development of potent inhibitors of the DNA-dependent protein kinase (DNA-PK)

Biography: Celine Cano studied Organic Chemistry at the University of Poitiers (France) where she received a Ph.D. degree in 2004 for her research on the synthesis of biomolecules by 1,3-dipolar cycloadditions with carbohydrates. In 2004, she carried out her post-doctoral work in the group of Professor John A. Joule at the University of Manchester working on the synthesis of analogues of cofactors of oxomolybdoenzymes. In 2005 she joined the Northern Institute for Cancer Research at Newcastle University as a research fellow, working with Professor Roger Griffin on the synthesis of inhibitors of DNA-dependent protein kinase (DNA-PK). She was appointed to a lectureship in Medicinal Chemistry at Newcastle University in 2008, promoted to senior lectureship in 2013, and has since played a key role in helping to establish Newcastle as an internationally recognised centre for anti-cancer drug development. Celine was awarded the Elsevier Reaxys 2016 Prize for Medicinal Chemistry in recognition of her research into anticancer drug discovery. She is the academic lead for the Medicinal Chemistry and Chemical Biology Group within the School of Chemistry.

Abstract: The cellular response to DNA double-strand break (DSB) formation is an essential component of normal cell survival, following exposure to DNA-damaging chemicals (e.g. cisplatin and doxorubicin) and ionising radiation [1]. The serine/threonine kinase DNA-dependent protein kinase (DNA-PK) is a member of the phosphatidylinositol (PI) 3-kinase related kinase (PIKK) family of enzymes, and plays an important role in DNA DSB repair via the non-homologous end-joining (NHEJ) pathway [2]. DNA-PK inhibitors may, therefore, be useful as agents to improve the activity of radio- and chemo-therapy in the treatment of cancer [3]. Identification of the lead benzo[h]chromen-4-one DNA-PK inhibitor NU7026 (IC50 = 0.23 uM), guided the subsequent development of the potent and selective ATP-competitive chromenone NU7441 (DNA-PK IC50 = 30 nM) [4]. Although proof-of-principle studies with NU7441 confirmed promising activity in vitro as a chemo- and radio-potentiator in a range of human tumour cell lines [5], further biological studies with NU7441 were hampered by sub-optimal pharmaceutical properties. In collaboration with AstraZeneca Pharmaceuticals, structure-activity relationship studies for DNA-PK inhibition by chromenone-derivatives were conducted in conjunction with homology modelling. This approach predicted several positions on the pendant dibenzothiophen-4-yl substituent of NU7441 as tolerant to substitution, without detriment to DNA-PK inhibitory activity. We will describe the rational design and syntheses of analogues that optimised the physicochemical and pharmacokinetic properties of NU7441. These studies resulted in the identification of compounds that combined potent DNA-PK inhibition with excellent aqueous solubility (20-40 mg/mL as acid salts), without compromising cellular activity. Prominent amongst these derivatives is KU-0060648 (DNA-PK IC50 = 8.6 nM), which exhibits 20-1000 fold selectivity for DNA-PK over related PIKK enzymes and PI3K family members. The discovery and further development of KU-0060648 and analogues will be described, including in vivo efficacy and combination studies [6-8].


Keynote Speaker

Jamal Mustafa
West Virginia University
USA

Title: Involvement of NADPH oxidase in Coronary Flow Regulation by Adenosine Receptors.

Biography: Dr. Jamal Mustafa is a Professor of Physiology and Pharmacology at West Virginia University (WVU). He has awarded with the Dean’s Award for Excellence in Research from SOM in 2008 and became a Robert C. Byrd Professor in 2010. And he also received Chancellor’s Award for Outstanding Achievement in Research and Scholarly Activities from HSC, in 2013. He has published more than 200 manuscripts. His past work has led to the approval of an A2A selective AR agonist (Lexican®) for myocardial perfusion imaging. Currently, they are using AR and β adrenergic receptor KOs to better understand the relationship between these receptors in coronary flow regulation.

Abstract: Adenosine increases coronary flow (CF) through the activation of A2A and A2B adenosine receptors (ARs).However, these mechanisms are not fully understood. We previously showed that adenosine-induced increase in CF is in part through NADPH oxidase (Nox), which is independent of A1 orA3 ARs. In this study, we hypothesize that adenosine-mediated increase in CF is through Nox activation and depends on A2A but not on A2B ARs. Functional studies were conducted using Langendorffmouse hearts. Hydrogen peroxide (H2O2) production was measured in isolated coronary arteries from WT, A2A andA2BAR KO mice using immunofluorescence. Adenosine-induced concentration-dependent increase in CF was attenuated by the specific Nox2 inhibitor gp91 ds-tat or reactive oxygen species (ROS) scavenger EUK134 in both WT and A2B but not A2A AR KO hearts. Similarly, the A2A AR selective agonist CGS-21680-induced increase in CF was significantly blunted by Nox2 inhibition in both WT and A2B AR KO, while the A2B AR selective agonist BAY 60-6583-induced increase in CF was not affected by Nox2 inhibition in WT. In intact isolated coronary arteries, adenosine-induced (10 μM) increase in H2O2 formation in both WTand A2BAR KO mice was attenuated byNox2 inhibition, whereas adenosine failed to increase H2O2 production in A2A AR KO mice. In conclusion, adenosine-induced increase in CF is partially mediated by Nox2-derivedH2O2, which critically depends upon the presence of A2A AR. These studies may lead to better understanding of the role of ARs in coronary disease and may lead to better therapeutic approaches.


Keynote Speaker

Kamal Omer Abdalla
University of Gadarif
Sudan

Title: Controlling of Blood Sugars and Lipids with Sudanese Dromedaries’ Camel Milk

Biography: Prof. Kamal Omer Abdalla has earned his PhD in Molecular and Cell Biology at the University of Cape Town in South Africa during the period of 2005-2009 and master’s diploma (1988-1993) in biology-biochemistry at Saint-Petersburg State University in Russia, certificate in clinical biochemistry at the Russian Academy for Advance Medical Studies in Moscow (1993-1995), two certificates in migration management and protection and migration and development (2015) respectively at the University of Maastricht and the UN University in Maastricht in the Netherlands and mini-master in ISO fundamental and internal audit (2016) at American Institute for Personal Development through 7th Vision Centre for training in Sudan. Currently, he is working an Associate Professor of Biochemistry & Molecular Biology in the Faculties of Medicine and Health Sciences, Medical Lab Sciences and Nursing at the University of Gadarif in Sudan and director of Directorate of Scientific Research & External Relations and Head of Biochemistry Dept at the University of Gadarif in Sudan. He has been successfully achieving these Administrative responsibilities. His research has included investigation of Sudanese natural medicines to treat various chronic human diseases including Diabetes Mellitus and lipid disorders, application of proteomics technology to investigate biomarkers in plant and animal tissues and studying of social and health problems. Based on this research and fellowship trainings he has received several awards and honors, such as scholarship funded by the Int’l Organization for Migration to study in the University of Maastricht and 7 prizes awarded by Sudan Ministry of Higher Education & Scientific Research and the University of Gadarif for his valuable contribution in the authorship of books that directly address current needs and problems of contemporary communities, permanent residence permit in the Republic of South Africa under the category of extraordinary skills, UCT international academic scholarship for academic merits, research bursary by the Molecular & Cell Biology department of the UCT, full scholarship to study in the former Soviet Union for Master’s Diploma, cash prize in intermediate school for talented pupil, membership of the International Commission on Scientific Signs in Qur’an and Sunnah of the Muslim World League, sponsored member of the American Association for the Advancement of Science during the period 2008-2010. He is serving as an editorial and advisory board member of several reputed Journals like the International Journal of Sudan Research, Merit Research J. of Medicine & Medical Sciences, Journal of Science Reports-Takshila, and University of Gadarif Journal of Science & Humanity. He has authored over 70 research articles and 7 books. Prof. Kamal Omer Abdalla has earned his PhD in Molecular and Cell Biology from the University of Cape Town, South Africa and master’s diploma in biology-biochemistry from Saint-Petersburg State University, Russia. Currently, he is working as an Associate prof. in the faculties of Medicine and Health Sciences & Medical lab Sciences and Nursing. He holds the director position of Scientific Research and External Relations & Head of Biochemistry Department at the University of Gadarif, Sudan. His research has included investigation of Sudanese natural medicines to treat various chronic human diseases including Diabetes Mellitus and lipid disorders, application of proteomics technology to investigate biomarkers in plant and animal tissues and studying of social and health problems. His contribution in this field led to the receipt of many awards and honors. And he is also serving as editorial and advisory board member of several reputed journals like International Journal of Sudan Research, Merit Research J. of Medicine & Medical Sciences, Journal of Science Reports-Takshila, and University of Gadarif Journal of Science & Humanity. He has authored over 70 research articles and 7 books.

Abstract: Diabetes mellitus (DM) incidences are in an increase with high prevalence rates in the world and in Sudan in particular. The disease is a leading cause of mortality, morbidity and economic loss worldwide. In Sudan, diabetes mellitus is being responsible for 10% of hospital admission and mortality. Till now, there is no drug that has been shown to modify the course of diabetic complications. Therefore, it is urgently needed to search for safe and more effective therapies for DM, either as complementary or alternative to existing treatment programs. Studies carried out on camel milk to explore its effects in the treatment of DM have proven that, camel milk is effective in control of hyperglycemia, lipid metabolism, regeneration of damaged beta-cells of the pancreas and absence of DM among camel nomads who commonly consume camel milk. In this study, the efficacy of raw camel milk on insulin doses, blood sugars, glycated hemoglobin (HbA1c), blood lipids and body mass indices in 30 patients of type 1 DM from the Diabetic Centre of Gadarif Pediatrics’ Teaching Hospital in the East of Sudan were evaluated. This is a 12-month (2 months monitoring period and 10 months trial period) randomized, open case control, parallel design study. The patients were divided into two groups. Group 1, the control group (N=15) received usual care (diet, exercise and insulin) and group 2, the study group (N=15) received 500 ml camel milk for 10 months in addition to usual care. Throughout the 12-month study period, blood sugars were measured weekly to maintain euglycemia by titrating the doses of insulin. Glycated hemoglobin and body mass indices were estimated at the beginning of the study and every 3 months until the end of the study. Lipid profile was estimated at the beginning of the study and every 15 days until the end of the study. Baseline data of both the groups were similar in demographic and variables. Camelus dromedary’s milk has reduced the doses of insulin by 46% for the study group after 4 months of consumption. Camel milk has shown significant hypoglycemic effects; it has reduced fasting blood sugar by 67% and postprandial blood sugar by 65%. Also, camel milk significantly improved HbA1c that has been reduced by 37%. Camel milk has shown significant positive effect on lipid metabolism of the study group. It has reduced total cholesterol by 35% since the 4th month consumption and has increased HDL by 236.5% after 3-4 months consumption, and it has reduced LDL by 78% after 3 months consumption and has reduced the VLDL by 33% after 3 months of consumption, and it has reduced the TGs by 33% after 4 months consumption. Also, camel milk has shown good positive effect on the BMI of the study group, it has improved the BMI for the group by 18% after 9 months consumption. On the other hand, comparative statistical analysis of the clinical variable parameters for the control group at the beginning of the study and by the end of it has shown no significant differences. This study has clearly demonstrated that camel milk is efficient in the reduction of the doses of insulin required to maintain long-term glycaemic control, and in controlling of blood sugars and lipids and in improving of BMI in type 1 diabetic patients. Based on these results, camel milk consumption may be therefore considered as a useful adjunct to parenteral insulin administration in the management of type 1 DM and in improvement of lipid metabolism and BMI. However, for greatest benefits from the Sudanese dromedary’s camel milk by the local communities and for better understanding of its therapeutic qualities and characteristics in the treatment of DM and prevent its complications further steps and studies are needed that should include: raising the awareness of the Sudanese communities about the health benefits of the camel milk and encourage diabetic patients especially children to consume camel milk, conduct more clinical trials on type 1 and type 2 DM on human and animals with larger sample sizes and compare the findings with the existing ones, and finally, conduct detailed analysis to identify and characterize the composition and chemical constituents of Sudanese dromedary’s camel milk. To our best knowledge this is the first study that has been conducted in Sudan to provide comprehensive insight into the effects of Sudanese raw camel milk on insulin doses, glycemic control, lipid metabolism and BMI of type 1diabetic patients.


Keynote Speaker

Jan Kyselovic
Comenius University
Slovakia

Title: Therapeutic modulation of miRNAs expression in human end-stage failing heart

Biography: Prof. Jan Kyselovic, PharmD, PhD holds professor position of pharmacology and chair of postgraduate PhD course for Pharmacology in Comenius University Bratislava, Slovakia. He is EU expert for EMA and alternant for Commission for Advanced Medicines. He was Research Fellow at Ottawa University, Canada and UCL Brussels, Belgium. He is emeritus dean of Faculty Pharmacy. His innovations in this field led to the receipt of the more than 7 international and 14 domestic grants and he leads a team of 15 scientists (7 PhD students). He has been supervisor theses for more than 150 students, and authored/co-authored over 80 peer-reviewed full articles, 2 books co-author, 2 book co-editor and 6 text books.

Abstract: The aim of our work was to analyse of „cardiac myosin switching” via gene expression of myosin heavy chain isoforms and role of microRNAs in failing hearts in correlation with pharmacotherapy. In the heart, three distinct isoforms MYH6, MYH7, MYH7B coexist in delicate balance. Patients with terminal-stage heart failure (n=40), indicated for heart transplantation. The follow clinical data from hospital records we collected: age, sex, BMI, blood pressure, type of heart failure (DCM, CAD, RCMP, AS, ECG, ECHO catheterization data, serum biochemistry, coexisting and pharmacotherapy. We examined samples from left ventricles of explanted hearts. In adult human failing hearts, we found the slow-twitch myosin heavy chain MYH7 (~98%) to be the predominantly expressed isoform whereas fast-twitch MYH6 isoform constitutes just about 1% of all myosin isoforms. The consequent change from fast-twitch alpha-isoform to the slow-twitch beta-isoform (known as myosin switching) could be one of the main causes of heart failure. Low expression of miR-208a and increased miR-208b has a significant correlation with expression contractile apparatus MYH6 and MYH7 of the heart, with significant discrepancy between expression alpha-myosin and miR 208a in explanted heart vs control ones. There is possibility of involving MYH7B and miR-499 with myosin switching. miR-1 and miR-133a seems to be in close relation with other cardiac microRNAs included in this study. The pharmacotherapy with beta-blockers increase the expression of all myosin isoforms. Conclusively, dysregulated gene expression of myosin heavy chains resulting in MYH7 upregulation and MYH6 downregulation might be pathological adaptation in heart failure is regulated through a complex net of relationships between MHCs – transcription factors – epigenetic modulators, but probably no microRNAs and is influenced by beta-blockers therapy.


Drug discovery & development

Session Introduction

Haleden Chiririwa
Vaal University of Technology
South Africa

Title: Synthesis and Characterisation of Palladium, Platinum and Gold complexes and their Biological activity against Oesophageal cancer cell lines

Biography: Harry completed his PhD in Synthetic Organometallic Chemistry at the University of Cape Town in 2010. He joined the Research Centre for Synthesis and Catalysis (Department of Chemistry) at the University of Johannesburg in January 2011 before moving to the Department of Chemical Engineering at the same institution in 2013. In 2015 he joined the Vaal University of Technology RSA after a stint at the National University of Science & Technology in Zimbabwe. His research work entails development of new methodologies for the synthesis of organometallic complexes and their applications in both medicine and catalysis and main interest is on utilizing and developing inorganic chemistry as a tool to answer questions arising in biomedical and biological disciplines. Most recently he has been involved in wastewater treatment and characterisation and synthesis of nanoparticles as potential candidates for a wide range of uses in the chemical industry. Harry has published more than 35 papers in international journals and conference proceedings and is also an active reviewer of accredited scientific journals and external examiner of MSc and PhD theses. He also serves on the Journal Scientific Board of Civil & Environmental Engineers (International Journal of Research in Chemical, Metallurgical and Civil Engineering (IJRCMCE) and is also a Committee member of the Scientific and Technical Committee & Editorial Review Board on Civil and Environmental Engineering (World Academy of Science, Engineering and Technology) WASET.

Abstract: New iminophosphine ligands were synthesised in good yields from the condensation of N-(2-(diphenylphosphino)benzaldehyde with the appropriate amine. All the ligands were fully characterised using spectroscopic and analytical techniques, including melting point, 1H, 13C, 31P NMR, MS, IR spectroscopy and elemental analysis. A series of new metal complexes (Pd, Pt and Au) were obtained by coordination of the iminophosphine ligands in good yields. The complexes were characterised using the spectroscopic and analytical techniques mentioned above, with the exception of the palladium dichloride complexes that are highly insoluble in organic solvents. The structures of three palladium complexes; three platinum complexes and three gold complexes were unambiguously determined using X-ray crystallography. The metal complexes were evaluated for their cytotoxicity against the oesophageal cancer cell lines WHCO1 and KYSE450. Platinum and gold complexes block the proliferation of WHCO1 and KYSE450 cells with an IC50 range of 2.16 - 9.44µM. The platinum and gold complexes exhibited better activity than cisplatin, while the chloromethyl palladium complexes were moderately active and exhibited IC50 values in the range 10.99 – 68.54µM for both cell lines. Our results show that these metal complexes have little effect on normal fibroblast cells (DMB) exhibiting IC50 values > 100µM which shows that these novel complexes are selective towards oesophageal cancer cells.


Helen Sheridan
Trinity College Dublin
Dublin

Title: The development of PH46A: from discovery to Phase 1 trials

Biography: Associate Professor and Director of Research, School of Pharmacy and Pharmaceutical Sciences, Trinity College Dublin. I am inspired by Natural Product Chemistry and Ethnomedicine. My goal is to translate my research from conception/ discovery to clinical use and find new therapies for diseases with unmet clinical need. In 2014 my first drug entered human clinical trials. I have learned a lot about the challenges and obstacles on the journey from discovery to humans. Experience-led decision making about research is invaluable and it is through this lens that I continue to pursue my research.

Abstract: The indane pharmacophore is a privileged structure of key importance in the natural world1. It is incorporated into diverse chemical scaffolds isolated from a range of organisms. Many indanes are now in clinical use1. Onychium ferns have been used in Traditional Medicine in Asia. In Nepal and Bangladesh extracts are used to treat fever in Bangladesh and dysentery; in India dysentery and hair loss2-3. Onychium siliculosum is used in Taiwanese folk medicine, and early studies looking at inhibition of contraction of isolated guinea-pig ileum have identified the active as the indanol Onitin, a non-specific smooth muscle relaxant which inhibits both D and M receptors of 5-HT4-5. The origins of the current study lie in the bioactivity of these and other monomeric indanes, present in the Onychium and Pteridium species of fern. Our early studies established smooth muscle relaxation and mast cell stabilisation effects for a range of these compounds6-9. An observation that dimeric indane molecules are significantly more potent mast cell stabilisers than their monomeric precursors10-11 led us via an synthetic medicinal chemistry programme to the identification of a lead anti-inflammatory clinical candidate, PH46A (2). PH46A underwent GMP synthesis in a number of international sites, this material then progressed through preclinical safety and toxicology studies and has now completed Phase 1 human clinical trials. The primary in vivo indication for PH46A is the treatment of Inflammatory Bowel Disease12, 13.


Sunday O. Okoh
University of Fort Hare
South Africa

Title: The effects of Azadirachtaindicasecondary metabolites on the antimicrobial, radical scavenging and cytotoxic propertieson herbal neem cream and soap.

Biography: Will be updated soon...

Abstract: Aim: The effects ofAzadirachtaindicasecondary metabolites (AISM) on neem soap and cream for management of infectious and oxidative stress diseases (OSD) were investigated in vitro. Methodology:Essential oils (EOs) wereobtained by modified Clevenger apparatus and AISM elucidated by GC-MS, GC/FID and retention index, while the radicals scavenging, antimicrobial and cytotoxicity of the neem cream (NMC) and soap (NMS) without and with the AISM were examined by spectrophotometric, micro-dilution and hemolytic techniques respectively. Results: Both cosmetics without AISMs exhibited bacteriostatic effects (BEs) against three reference bacterial strains (Staphylococcus aureus,Listeriaivanovii, Enterobacter cloacae) and two confirmed multi-drug resistant bacterial strains(Vibrioparaheamolyticues, Escherichia coli 180) at dose less than 0.31mg/mL. Similar BEs were observed against two clinical dermatophytes and two reference fungal strains at <0.50 mg/mL,while the NMS with the AISMs demonstrated bactericidal effects on most of the test pathogens linked to infectious diseases. The neem soap with AISMs displayed noteworthy effects in scavenging radicals associated OSD below 1.76 mg/mL. The cosmetics were not toxic on human red blood cells below 0.850 mg/mL. To our known, the AISM predominantly caryophyllene (30.02%), phytol (14.12%) and elemene (13.40%),exceptional modulating effects in neem cosmetics are reported here for the first time.Conclusion: The study indicates that apart from tradition uses of A.indica, the EOs contained very potent secondary metabolites and possible new antimicrobial agents, as well as alternative to synthetic antioxidant, likewise considered useful in pharmaceutical, cosmetics industries and as food preservatives. Keywords: Azadirachtaindica, secondary metabolites, bioactivities, neem cosmetics Graphic image Figure 1: Radicals scavenging effects of Azadirachtaindica secondary metabolites of neem cosmetics and reference compounds on radicals associated with degenerative diseases. Acknowledgement The authors are grateful to the South Africa Medical Research council, GMRDC, National research foundation South Africa, Federal Institute of Industrial, Lagos and University of Fort Hare, South Africa for financial support. References Hamid et al. 2011. Essential oils: Its medicinal & pharmacological uses. Inter. J. Curr. Res. 2011,33(2): 086-098. Morten et al. 2012.Essential Oils in Food Preservation: Mode of Action Synergies and interactions with food matrix components. J. Front. Microbiol.2012, 3, 12.


Jean-Luc Galzi
Université de Strasbourg
France

Title: Decoy chemokine ligands with an anti-inflammatory activity

Biography: Will be updated soon...

Abstract: Excessive signaling by chemokines has been associated with chronic inflammation or cancer, thus attracting substantial attention as promising therapeutic targets. Inspired by chemokine-clearing molecules shaped by pathogens to escape the immune system, we designed a generic screening assay to discover chemokine-neutralizing molecules (neutraligands) and unambiguously distinguish them from molecules that block the receptor (receptor antagonists). This assay, called TRIC-r, combines time-resolved intracellular calcium recordings with pre-incubation of bioactive compounds either with the chemokine or the receptor-expressing cells. We describe the identification of high affinity neutraligands of CXCL12, CCL17 and CCL22, three chemokines involved in Th2-type inflammations. The decoy molecules inhibit in vitro chemokine-induced intracellular calcium responses, CCR4 and CXCR4 endocytosis and human T cell migration. In vivo, they inhibit inflammation in several models of inflammation such as asthma or atopic dermatitis, in particular they block the recruitment of eosinophils, dendritic cells and CD4+T cells. Their mechanism of action and long lasting effects will be described in details from the in vitro up to the in vivo level.


Hanny Ibrahim
Egyptian Russian University
Egypt

Title: Albumin bound nanoparticles in the treatment of malaria

Biography: Dr. Hany IBRAHIM obtained his master degree, in 2004, from Reims University and his Ph.D., in 2008, from Toulouse University, France. Immediately after, he worked as a researcher at Pharma-Dev laboratory in Toulouse till 2012. In 2013, he worked as consultant in Baxter R&D, Belgium. In 2014, he worked as assistant professor, at the faculty of Pharmacy, Toulouse III University. In 2015, he joined the Egyptian Russian University in Egypt where he serves as the head of Analytical Chemistry Department. Major research points focused on the development of nanoformulation of new drug candidates alongside with the development of new analytical strategies to follow up the drug at different stages during drug discovery (from chemical synthesis to formulation & in vivo post-administration). He had two patents (international & European) and many publications in international journals. He won two French awards, in 2010 “young researcher award” from Foundation for Medical Research and in 2013 “young investigator award” from Toulouse institute of Chemistry.

Abstract: Nanoparticles have been used recently to improve drug dissolution rate, saturation solubility, bioavailability and hence efficacy. Various macromolecular substances have been used for the preparation of biodegradable nanoparticles. Among these, human serum albumin (HSA) has proved to be a promising drug carrier due to its endogenous, non-toxic, non-immunogenic and surface-active properties that can improve drug wettability and bioavailability and decrease particle aggregation. HSA can target malaria-infected erythrocytes as it is selectively taken up by parasitized RBCs [1]. HSA is the only adjunctive therapy that was associated with a reduction in mortality in severe and cerebral malaria [2]. All these factors make human serum albumin an ideal candidate for antimalarial drug delivery. Albumin bound nanoparticles of artemisinin and indolone-N-oxide derivative have been prepared by precipitation followed by high pressure homogenization. The nanoparticles have been fully characterized and evaluated in in-vitro & in-vivo against murine and “humanized” mice models. Nanoparticle analysis revealed the production of elongated homogenous, small size and highly stable nanoparticles suitable for intravenous administration [3-5]. The analysis of drug entrapment showed a high entrapment efficiency alongside with a good physical and chemical stability within albumin nanoparticles. This good chemical stability is explained by the fact that the drug is inserted in a hydrophobic region in albumin molecule thus protecting it from the external environment [6]. The formulation showed comparable antimalarial activities to reference drugs (artesunate and chloroquine) and was remarkably more effective in prolonging survival time and inhibiting recrudescence. Albumin-bound nanoparticles represent a new strategic approach to target malaria-infected erythrocytes. This organic solvent-free formulation, of practically water insoluble antimalarials, allows the intravenous administration of artemisinin for the first time. Furthermore, this technique was successfully applied to formulate ATRA (all trans retinoic acid) to target acute myeloid leukaemia [7].


Ofra Benny
The Hebrew University
Israel

Title: Rational design of nano-carriers for drug delivery in cancer

Biography: Dr. Ofra Benny is a senior lecturer and the head of The Lab for Nanomedicine and Tumor Microenvironment at the School of Pharmacy, and Faculty of Medicine in the Hebrew University. Dr. Benny’s lab focuses on cancer research and development of novel drug delivery systems for cancer therapy. He got her B.Sc and PhD in Biotechnology Engineering from the Technion, Israel and her postdoctoral was in the Vascular Biology Lab of Prof. Judah Folkman at the Boston Children’s Hospital, Harvard Medical School. During her postdoctoral Dr. Benny developed an oral nanoformulation for an anti cancer drug.

Abstract: Controlling the interaction of drug delivery systems (DDS) with biological tissues is critical for the success of therapies. Specifically in cancer, due to the high density of the tumors, tissue penetration of DDS is critical and may be challenging. We showed that polymer micelles can be used efficiently to deliver small molecule drugs into cancer cells and tissues. Our recent work, published in JCR (1) study the effect of mechanical cues of drug vehicle on their interactions with tumor cells and tissue-like 3D structures ex-vivo. Using polymer micelles we compared flexible Wet Polymer Micelles (WPM) to semi-solid Solidified Polymer Micelles (SPMs) for their physiochemical properties and their interactions with cancer cells. For that we have performed detailed characterization of SPM compared to WPM, including examinations of particle size, stability, drug release kinetics and cell transcytosis, in melanoma A-375 cells. Cell uptake measurements were done using FACS and microscopy imaging, showing enhanced abilities of SPMs to penetrate cells and tissues. A simple physical model is presented that well agrees with the experiments and provides insight about the role of particle rigidity in the engulfment mechanism. We conclude that particle rigidity enhances cellular uptake and tissue penetration and that SPMs have promising potential as an effective and highly permeable DDS. Our findings can be important in future rational design of DDS for particle adjustment to specific tissues and pathology. Ref: J Control Release. 2016 Dec 23. pii: S0168-3659(16)30783-0.


Maria Taskova
University of Southern Denmark
Denmark

Title: Bioconjugated Oligonucleotides as Specific and Stable Gene Therapeutics with High Potential for Intracellular Delivery

Biography: Ms. Maria Taskova is a PhD fellow at the University of Southern Denmark. She studied Pharmacy at the Saint Cyril and Methodius University and she got her Mr. Ph. Degree in 2013. Afterwards, she carried out Master program in chemistry, studying Novel peptide-oligonucleotide conjugates and their properties and she gained her second M.Sc degree in Chemistry at the University of Southern Denmark under the supervision of Prof. Dr Kira Astakhova. Currently as a PhD student in the laboratory of Dr. Astakhova, her research interest is interdisciplinary combining organic chemistry, biochemistry, biomedicine, biophysics nanobioscience and pharmacy. Her focus is on development of new gene therapeutics and new tools for ultra-specific targeting of nucleic acids.

Abstract: In this talk, Peptide-Oligonucleotide Conjugates will be presented as a promising class of gene therapeutics. In particular, their synthesis and studies of therapeutic potential will be discussed in detail.After couple of decades of intensive research, the high potential of synthetic oligonucleotides in the fields of personalized medicine has been confirmed. The mutual mechanism of action, i.e unique Watson-Crick base pairing, makes gene therapeutics applicable for numerous diseases starting with cancer, neurological diseases, viral and bacterial infections. However, in order to reach the clinic, synthetic nucleic acids therapeutics still have to meet the requirements of specific target binding, high resistance to enzymatic degradation and efficient intracellular delivery. Novel peptide-oligonucleotide molecules show improved target recognition and stability to enzymatic degradation which makes us believe that they have a high potential in future gene therapy.


HY Kim
Skin Science Laboratory
Republic of Korea

Title: Cynarin inhibits melanogenesis through ERK signaling pathway on α-MSH-induced Melanin Biosynthesis

Biography: Will be updated soon...

Abstract: Cynarin is composed of plant such as artichoke, sunflower seed and burdock. These materials have compound such as chlorogenic acid (caffeoylquinic acid), caffeic acid, cynarin (dicaffeoylquinic acid), quercitrin (quercetin rhamnoside), arctiin, quercetin, luteolin. They provide special bio-physiological effect: chlorogenic acid, caffeic acid, quercitrin and luteolin as anti-melanogenesis factor; arctiin as inflammatory regulator (MAPK related factor) or protector from UVB-induced stress and so on. However, it has not been reported yet for melanogenesis biosynthesis of cynarin as component of these plants. Therefore, we also investigated melanogenesis of cynarin via signaling pathway.Melanogenesis-related protein as MITF, tyrosinasewere decreased by cynarin via ERK signaling pathway in α-MSH-induced human melanoma cells (MNT-1). Cynarin was also represented inhibition of melanin content and intracellular tyrosinase activity. Cynarin is being provided at anti-melanogenesis or anti-pigmentation factors because of it investigated anti-melanogenesis mechanism in α-MSH-induced human melanoma cell and are well worth enough.


Zine Kechrid
University of Annaba
Algeria

Title: Effect of silymarin extracted from Silybum marianum on nickel hematotoxicity and nephrotoxicity in male albino wistar rats

Biography: Will be updated soon...

Abstract: The objective of this study was to investigate the effect of silymarin extract from Silybum marianum against nickel-induced alterations in haematological indices, kidney dysfunction and renal antioxidant defense system. Male albino wistar rats were divided into four groups seven each. Control, silymarin, nickel and nickel plus silymarin. Silymarin was administrated orally (100 mg/kg b. wt.) and nickel as nickel sulfate (NiSO4 6H20) was given intraperitoneally (20 mg/kg b. wt) at alternative days. The Experiment continued for three consecutive weeks. The treatment with nickel led to a significant decrease in body weight with an increase in both absolute and relative kidney weights and a significant increase in renal markers (creatinine, urea, and uric acid), which confirmed by histopathological alteration. A microcytic anemia was also observed, which was manifested by a reduction of red blood cells count (RBC), hemoglobin (Hb) concentration, platelet counts (Plt), hematocrit and white blood cells counts (WBC). The level of lipid peroxidation was increased. Whereas, GSH concentration and enzymatic antioxidants SOD, GSH-Px and CAT activities were decreased. The co-treatment with methanolic extract of milk thistle attenuated the variation in the hematological and renal markers, decreasing renal lipid peroxidation with a concomitant increasing reduced glutathione content and altering antioxidant enzymatic system in kidney, as well as an improvement in histological changes compared to those previously noticed in nickel group.To conclude, these findings demonstrated that silymarin extract effectively improved heamatotoxicity and nephrotoxicity caused by nickel.


Ethno pharmacology & Phytochemistry

Session Introduction

Samantha L. Gerlach
Dillard University
USA

Title: The plant derived peptide cycloviolacin O2 enhances anti-HIV efficacy by disrupting viral particles and increasing drug uptake

Biography: Dr. Samantha L. Gerlach received her PhD in the Department of Ecology and Evolutionary Biology at Tulane University (TU) and completed postdoctoral research in the Pharmacology Department (TU). Her research focuses on the discovery and therapeutic bioactivity of novel cyclotides that have been isolated from plants with a rich ethnomedical history. She is an Assistant Professor at Dillard University who teaches Botany, Conservation, Ecology, Research Methodology, and Basic Biology.

Abstract: Despite the availability of potent antiretrovirals (ARV) subtherapeutic drug entry into HIV-1 infected cells enable viral propagation and facilitate the selection of drug resistance. Resurgence in plasma viremia, occurring during the time needed for drug susceptibility assessment in the clinic, causes the development of newly infected reservoir pool. Therefore, novel adjuvant strategies that increase ARV efficacy and suppress the resurging viral load will be of significant value in patients. The membrane targeting effect of plant derived cyclotides and their ability to specifically recognize phosphatidyl-ethanolamine (PE) enriched lipid membranes provides a promising approach, to simultaneously increase drug entry and cause viral particle disruption. The lipid envelope of HIV particles is rich in PE, and the plasma membranes of productively infected cells are enriched with raft-like regions containing these phospholipids. The prototypic bracelet cyclotide, Cycloviolacin O2 (CyO2) has a strong affinity to PE-rich membranes and shows high efficiency in membrane destabilization. Therefore, we investigated if low doses of CyO2 can be used to form multimeric pores in HIV-1 infected cells in order to increase ARV uptake, and whether low dose CyO2 can also directly target the HIV-1 envelope to disrupt the infectivity of viral particles. Fluorescent dye (Sytox-green) uptake assays showed that subtoxic concentrations CyO2 (<0.5 M) rapidly increased pore-formation in productively infected T-cells (HuT78 and PM1) and monocytes (U1). CyO2 coexposure rapidly enhanced the intracellular levels of a radiolabeled HIV-1 protease inhibitor (HPI), tritiated saquinavir [3H-SAQ]. In both short-term (2-6 h) and long-term (72 h) exposure studies, CyO2 increased (p<0.05) the antiviral efficacy of two HPIs, SAQ and nelfinavir (NEL) as evident by decreased HIV-1 p24Gag levels in culture supernatants (by ELISA). Pore-formation by CyO2 was significantly lower in the uninfected cells and primary endothelial cells, implicating specificity for infected cell membranes. Interestingly, a subtoxic dose of CyO2 was also effective in suppressing HIV-1 infection and p24 production by itself (p<0.05). Mechanistic studies were first carried out to determine the effect of CyO2 on proviral gene expression via the HIV-1 LTR. In two cell lines, J-Lat (T-cells) and U937-VRX (monocyte), containing an integrated provirus that directs GFP reporter expression, CyO2 did not suppress HIV-1 LTR function. However, studies using a replication defective viral like particle (VLP) that expresses GFP following infection and chromosomal integration, clearly indicated that CyO2 suppresses the infectivity of VLPs. CyO2 exposure of cell-free virus (CFV) followed by ultracentrifugation to pellet intact viral particles showed a direct effect of CyO2 in disrupting infectious virions. Significant decreases in internal viral contents (p24 protein and viral RNA) and decreased infectivity of the viral titer were evident following exposure to CyO2 alone. Pre-exposure to CyO2 (<0.5 M) suppressed viral infectivity in PM1 cells (p<0.05) and enhanced (p<0.05) antiviral efficacy of the HIV-1 entry inhibitor, Enfuvirtide. Thus, adjuvant treatment with subtoxic doses of CyO2 may be a promising strategy in HIV-positive patients.


Rogelio Pereda-Miranda
National University of Mexico
Mexico

Title: Reversal of Multidrug Resistance by Morning Glory Resin Glycosides in Bacterial Pathogens and Human Cancer Cells

Biography: Will be updated soon...

Abstract: Resin glycosides are complex amphipatic glycolipids of high molecular weight derived from species of the morning glory family (Convolvulaceae). The modulatory effect of microbiologically inactive resin glycosides, evaluated on nosocomial multidrug-resistant (MDR) Gram–positive (Staphylococcus aureus) and –negative (Salmolella typhi and Shigella flexneri) microorganisms, led to the characterization of theses compounds as substrates for efflux pumps. Resin glycosides (25 g/mL) exerted a potentiation effect on clinically useful antibiotics against the selected tested pathogens by increasing antibiotic susceptibility up to 64-fold. Reversal of MDR by these metabolites was also evaluated in vinblastine-resistant human breast carcinoma cells (MCF-7/Vin). The active non-cytotoxic compounds exerted a potentiation effect on MCF-7/Vin susceptibility to vinblastine over 1906-fold when tested at concentrations of 5 and 25 g/mL. Through flow cytometry, resin glycosides significantly increased the intracellular accumulation of rhodamine 123 (a substrate for P-glycoprotein, a mammalian effluxing pump). After incubation with a monoclonal antibody, immunofluorescence flow cytometry was used to detect a decreased expression of P-gp by resin glycosides. These results suggest that morning glory oligosaccharides represent potential efflux pump inhibitors for overcoming refractory malignancies by lowering the doses of drugs in combinatorial therapy.


Mahboob Alam
University of Lahore
Pakistan

Title: Bioassay-guided isolation of new urease inhibitors from Ferula narthex Bioss

Biography: Will be updated soon...

Abstract: The current study was designed to evaluate the urease inhibitory activities of fractions of Ferula narthex Bioss followed by bioassay guided isolation of new urease sesquiterpene coumarins, as potential urease inhibitors. The chloroform and ethylacetate frictions were found significantly active against urease enzyme with IC50 values of 42.5 ± 1.72 and 169.3 ± 2.54 μg/mL, respectively. Upon fractionation of chloroform the compounds 2-5 were isolated and compound 1 was isolated from ethylacetate. The compounds 2, 3 and 5 demonstrated good urease inhibition with IC50 values in range of 116 ± 1.29- 464.43 ± 5.50 μM. Molecular docking studies of active compounds (2, 3 and 5) were carried out, in order to know the binding mode of interaction and energy minimization in the active site of urease. In short, both the extract/fractions and isolated compounds showed marked urease inhibition and thus could a useful natural source of urease inhibition. Key words: Ferula narthex, sesquiterpene coumarins, urease inhibitory activity, molecular docking


Zouhir Djerrou
University of Mentouri Constantine
Algeria

Title: Assessment of anti-hyperlipidemic effects of Pistacia lentiscus fatty oil in egg yolk-fed rabbits

Biography: Dr. Zouhir Djerrou is an Algerian researcher born in August 1976. He was an Associate Professor at the Institute of Veterinary Sciences, University of Mentouri Constantine, Algeria. He is currently an Associate Professor at Department of Nature and Life Sciences, Faculty of Sciences, University of August 20th 1955 (Algeria) since October 2014. He is the team leader of “Toxicology” since 2013 in the Laboratory of Pharmacology and Toxicology at Mentouri Constantine University. He has reviewed a lot of citation-indexed journal articles submitted for publication in international journals. He has participated in several scientific projects in the field of Pharmacology and toxicology. His work is mainly focused on pharmaco-toxicological profiles of medicinal plants with added value.

Abstract: The current study was undertaken to assess anti-hyperlipidemic activity of Pistacia lentiscus fatty oil (PLFO) in rabbits following a hyperlipidemic diet. Twenty healthy female (WNZ) rabbits were divided into four groups of five animals each: (a) normal control (NC group) receiving standard diet, (b) hyperlipidemic control (EY) group receiving standard diet and gavaged daily with egg yolk (10 mL), (c) hyperlipidemic + PLFO (EY + PLFO) group receiving as the EY group and treated daily with PLFO (2 mL/kg BW, (d) hyperlipidemic + simvastatin (EY + SVS) group receiving as the EY group and treated once daily with 2.5 mg/kg BW of simvastatin. At the end of the six-week experimental period, the lipidemic profiles of the different groups were investigated. In the EY group, the egg yolk resulted in a significant increase of total cholesterol (TC), triglycerides (TG), HDL-C, LDL-C, and the LDL-C/HDL-C ratio. Both the EY + PLFO and EY + SVS groups, when compared to the EY group, showed a significant decrease of TC, TG, LDL-C, and the LDL-C/HDL-C ratio. However, with respect to HDL-C the differences were not significant. The TGs were significantly lower (P < 0.001) in the simvastatin-treated group when compared to rabbits treated in the PLFO group. The study concludes that P. lentiscus fatty oil possesses anti-hyperlipidemic properties at least in reducing total cholesterol, LDL-cholesterol and triglycerides.


Ikpesu T.O.
Federal University Otuoke,
Nigeria

Title: In - vivo screening of the extract of Solenostemon monstachus and Ocimum gratissimum for the treatment of type 2 diabetes

Biography: Dr.Ikpesu Thomas Ohwofasa, was born on the 15th June, 1979 in Ile- Ife, Osun State Nigeria. He hailed from Okpara Inland in Ethiope East Local Government, Delta State Nigeria. he has a PhD in pharmacology from University of Benin, Benin City Nigeria. He is a member of the Society of Environmental Toxicology and Chemistry and an Associate Editor of International Journal of Basic Science and Technology. He has published papers both in Local and International Journals and attended Conferences both locally and internationally. He currently working on therapeutic plants and bioremediation. A staff of Federal University, Otuoke Nigeria

Abstract: Diabetes is one health challenge that can retrict someone the benefit of a smooth and promising life. It is a costly disease, placing a high financial burden on the patient and the healthcare system. If poorly managed or left untreated, it can cause blindness, loss of kidney function, and conditions that require the amputation of digits or limbs. To avoid these complications we investigated the efficacy of the mixture of a locally use herbs use for the management of the condition in Africa; Solenostemon monstachus and Ocimum gratissimum. The investigation was in two phases;the first phase involve the use of zebra fish, while 25 volunteers human were studied in the second phase. The fishes were induced with diazinon ( a chemical that causes hyperglycemic in animal and human). After 96 hours, the they were transfered to a distillated water. The control fish were not treated with the herb but hyperglycemic with the diazinon. To obtain more significant results, blood sugar responses were monitored at different times after administration of herbs mixture at different dosages . The fish were not fed during this period. In each cases, the changes in the different treatments were compared with the control. All the doses of the herb gave a positive results (range between 45-112mmol/L). The human volunters with ascertained medical records and are suffering from type 2 diabetes were given the dose that maintained the sugar level between 75-85mmol/L thrice daily. The volunters were adviced to eat without restriction for 96 hours. At the end of the investigation, their sugar level were measured. The sugar level of the patients ranged between 61-89mmol/L, which is within the normal range. This findings revealed the efficacy of these herbs and holistics investigation of the efficacy of these plants mixture is inevitable, and if harness it will reduce the conscientiousness attached to diabetes in our society


Bikash Shrestha
Nepalese Army Institute of Health Sciences
Nepal

Title: ANTENATAL STEROIDS-WHERE ARE WE

Biography: Will be updated soon...

Abstract: Antenatal steroids-Where are we
Parts of presentation
History and evolution of steroids for preterms
The evolution of consensus for antenatal steroids
Established surrent recommendation
New studies of steroids of late preterm and term and coming up recommendations
Use of antenatal steroids all over the world


Jasia Bokhari
Shaheed Zulfiqar Ali Bhutto Medical University
Islamabad

Title: Cardio protective effect of Digera muricata (L) Mart. against the cardiotoxicity induced by acrylamide in rats.

Biography: Will be updated soon...

Abstract: The aim of present study was to investigate the cardioprotective effect of Digera muricata (L) Mart. against the cardiotoxicity induced by acrylamide in rats. Forty eight healthy female albino rats, weighing 190-200 g, divided into eight groups with six rats in each grooup I as control, while group II and were administered with dimethylsulphoxide (DMSO) 5.0 ml/kg b.w. orally once a day for four weeks. Group III was given 200 mg/kg b.w. of methanolic extract dissolved in DMSO once a day for four weeks. Rest of the rats were divided into five groups and were treated with aqueous solution of acrylamide 6 mg/kg b.w. intraparetoneally once a day for two weeks. Group IV was sacrificed after 15 days of the acrylamide treatment to collect the serum and heart gland. Group V remained untreated as such for the rest of the experiment Group VI, VII and VIII were given 100, 150 and 200 mg/kg b.w. methanolic extract dissolved in DMSO once a day for two weeks. After four weeks all the animals were disected and the blood was collected by cardiac puncture and 5-7 ml blood was taken in falcon tube and was centrifuged to collect the serum and stored at -20ºC for biochemical studies. Cotreatment with Digera muricata extract at 100, 150 and 200 mg/kg prevented the elevation of serum marker enzymes creatinine kinase (CK), cardiac creatinine kinase (CK-MB), lactate dehydrogenase (LDH), aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), hydrogen peroxidase (H2O2), total cholesterol, LDL and alterations in protein, superoxide dismutase (SOD), peroxidase (POD), catalase (CAT), glutathione (GSH), glutathione-S-transferase (GST), Gluthaione peroxidase (GSHPx), γ-glutamyl transpeptidase (γ-GT), HDL, creatine and urea caused by acrylamide in rats. The protective effect was confirmed by the histological findings and was more prominent at 200 mg/kg. Hence we conclude that methanolic extract of Digera muricata protects against acrylamide induced cardiac toxicity.