Day 1 :
University in Catania, Italy
Time : 14:30-15:00
Rita Turnaturi achieved the PhD in Medicinal Chemistry from University of Catania. Currently she is performing a fellowship at the Department of Drug Sciences of University of Catania. She has published more than 30 papers in reputed peer-reviewed journals.
Opioid analgesics, such as morphine, elicit analgesic effects primarily through mu opioid receptor (MOR), whose activation determines not only analgesia but also a sequel of unwanted side effects. Although indispensable for the management of acute severe pain, the classical analgesics are unsuccessful for inflammatory and neuropathic pain treatment. Multitarget MOR/delta opioid receptor (DOR) agonists, showing synergic antinociceptive activity with low side-effects induction in preclinical models, represent a strategy to overcome the default in chronic pain treatment.
In this context, we identified the multitarget MOR/DOR ligand LP2 characterized by high MOR (Ki= 1.08 nM) and DOR (Ki= 6.6 nM) affinity coupled to an agonist profile versus these receptors (IC50MOR= 21.5 nM and IC50DOR= 4.4 nM). In tail flick test, LP2 produced a long-lasting antinociception naloxone-reversed (ED50 of 0.9 mg/kg i.p.). Building upon these evidences, our efforts were focused on demonstrating whether the LP2 multitarget profile could be useful for persistent pain states. Thus, LP2 is evaluated in a model of neuropathic pain induced by chronic constriction injury (CCI) and a model of inflammatory pain (Formalin test). Moreover, both 2R- and 2S- diastereoisomers of LP2 were synthesized in order to investigate the role of the stereocenter at the N-substituent of the 6,7-benzomorphan scaffold in drug-opioid receptor interaction. Their pharmacological profile were compared each other and with LP2. Specifically, 2S-LP2 showed an increased antinociceptive effect than LP-2 consistent with the in vitro functional profile. Moreover, 2S-LP2 resulted a biased MOR/DOR agonist with functional selectivity for G-protein signaling and reduced β-arrestin 2 recruitment, an effectiveness profile in chronic pain conditions management.
- Medicinal Chemistry and Drug Discovery | Medical Devices for Drug Delivery | Drug Delivery Chemistry | Anticancer Agents in Medicinal Chemistry | Drug Chemistry |Bioorganic Medicinal Chemistry | Applied Medicinal Chemistry
Arvind Gavali College of Pharmacy, India
Title: Isoniazid-phenolic acid co-drugs: Synthesis, pharmacokinetics and investigation of antimycobacterial and hepatoprotective potential
Time : 09:00-09:30
Neha V. Bhilare has completed her M.Pharm in Pharmaceutical Chemistry at the Bharati Vidyapeeth’s Poona College of Pharmacy, India in 2014. She recently received her Ph.D. degree from the same institution (Nov. 2019). She is currently associated with Arvind Gavali College of Pharmacy, India and is actively involved in research on prodrug design and development. She has published papers in SCI journals with good impact factors and also authored a chapter on “Prodrugs for Lipophilicity enhancement” (In book “Recent advancement in Prodrugs”-CRC Press Taylor and Francis Group, 2020).
Statement of the Problem: According to WHO statistics of 2018, there were an estimated 1.2 million TB deaths among HIV-negative people. Isoniazid is being used for more than 60 years in the treatment of this deadly disease, but emergence of resistance towards this drug and metabolic and morphological aberrations in the liver have raised serious concerns regarding its continued use in future.
Methodology & Theoretical Orientation: To overcome these hazardous effects, a novel hepatoprotective and antimycobacterial prodrug strategy was developed by combining INH with phenolic acids (gallic acid, syringic acid & vanillic acid) as antioxidant promoeities for probable synergistic effect. Prodrugs synthesized by Schotten Baumann reaction were characterized by spectral analysis and in vitro and in vivo release studies were carried out using HPLC. Their hepatoprotective potential was evaluated in male Wistar rats by performing the liver function tests, oxidative stress markers and histopathology studies. The antimycobacterial efficacy of prodrugs was examined in terms of its ability to decrease the lung bacillary load in Balb/c mice infected intravenously with Mycobacterium tuberculosis.
Findings: All the prodrugs were effective in abrogating oxidative stress and re-establishing the normal hepatic physiology. Especially the effect of prodrugs of INH with gallic acid and syringic acid in restoring the levels of enzymes superoxide dismutase and glutathione peroxidase and abrogating liver damage was noteworthy. The findings of antimycobacterial activity assessment evidently demonstrated that prodrugs were as potent as INH in lowering the mycobacterial load in mice.
National Institute of Pharmaceutical Education and Research Ahmedabad, India
Title: Computer assisted design, synthesis and biological evaluation of Thiazole based molecules as Bcl2 inhibitors
Time : 09:30-10:00
Sagarkumar Patel completed his B. Pharm from Ganpat University, Gujarat in 2014 and obtained M. Tech (Pharm) degree from the National Institute of Pharmaceutical Education and Research (NIPER), Mohali (India) under guidance of Dr. Joydev K Laha, in 2016. Now he is pursuing fourth Year Ph. D in department of Medicinal Chemistry in National Institute of Pharmaceutical Education and Research (NIPER)- Ahmedabad under the guidance of Dr. Amit Shard. Current his research area is designing and synthesis of kinase inhibitors/activators.
Introduction: With the emergence of chemo-resistance and vast cancer types, quest to design novel and potent anticancer molecules is always a priority to enrich the armamentarium of medicinal chemists. The antiapoptotic Bcl-2 proteins are significantly over expressed in several tumor types and are striking targets for therapeutic intervention. This is because once the recalcitrant Bcl-2 proteins are inhibited, the cell follows the regular pathway of apoptosis, that significantly halts tumor progression.
Method: Virtually designed molecules were subjected to rigorous in silico screening (docking and ADMET studies). The intuition verified by computation was confirmed by wet bench experiments. Here several thiazole based scaffolds were designed in 3 steps and in vitro evaluated against Bcl-2-Jurkat, A-431 and ARPE-19 cell lines.
Results: Among them molecules 32, 50, 53, 57 are 59 showed potent activities against Bcl-2 Jurkat cell line at concentrations ranging from 32-46 µM respectively. One of the ligands 32 emerged as most potent and was subjected to molecular dynamics (MD) simulation with death defying anti-apoptotic Bcl-2 proteins (4IEH). It was shown that 32 interacted with protein majorly via hydrophobic interactions and few electrostatic interactions were also observed. During the MD simulation conformational changes in Bcl-2 protein were observed that facilitates the movement of ligand inside the cavity of protein (majorly involving α3, α4, α5, helices) Flow cytometry analysis of compound 32 suggested that cell undergoes 87.66% Annexin A5 positive.
Discussion: This confirmed our hypothesis that rationally designed molecules validated by computational means can significantly target tumor cells and hits developed can be effectively converted into leads by downstream modifications.
Institute of Nuclear Medicine and Allied Sciences, India
Time : 10:00-10:30
Swastika is affiliated to Division of Cyclotron and Radiopharmaceutical Sciences, Institute of Nuclear Medicine and Allied Sciences, New Delhi.
Objective: The blood–brain barrier (BBB) is a major obstacle for drug delivery to the brain. Nucleolipid based liposomes are promising drug delivery systems allowing in vivo tracking using molecular imaging techniques and have proved promising theranostics agents especially for tumors. However, efficient liposomal preparations for theranostic of neuro-onco, neuro-infection and neurodegenerative diseases needs further research. Nucleolipidic liposomes (NL-Nps) are of great interest because of the site-recognition (nucleoside), lipophilicity (long alkyl chain) and better membrane translocation by interaction of fatty acid with the lipid bilayer. Thus, we have evaluated uridine derived nucleolipidic liposomes for encapsulation efficiencies of MTX (methotrexate) anti-cancer and sulfanilamide anti–infection drug and in vivo tracking by radiolabeling with 99mTc.
Materials and Method: (NL-Nps) were prepared using NL-DTPA (synthesized), heated to 50° C when mixed with organic solvent and added to aqueous phase containing the surfactant Tween-80 and the co-surfactant soya lecithin. NL-Nps were encapsulated with MTX and sulfanilamide were similarly prepared by adding drugs (0.1 to 1.5%) to the formulation. NL-Nps were evaluated for release kinetics and brain targeting in BMG-1 (brain glioma) and neuronal cell line in murine model.
Results: Multi-step synthesis leads to the final compound (NL-DTPA) and its liposomal preparation (size 113 to 130 nm, zeta potential -14 to -28 mV) with EEs of 64% was achieved. Liposomes showed sustained drug release for 2-5 days negligible hemolytic activity, no cytotoxicity in HEK cells. Radiolabeling efficiency of 98% was achieved using 99mTc conferring prolonged systemic circulation and renal route excretion. The biodistribution showed 1.8% ID/gm to 2.3% ID/gm for intact versus disrupted BBB in mice models. (NL-Nps) also in BMG tumor mice depicted higher tumor uptake (2.3T/M).
Conclusion: Nucleolipid functionalized liposomes as candidates to be used as biocompatible nanocarrier systems with high systemic retention and anti-tumour effects. Future work will concentrate on targeting of liposomes in brain tumor model using stereotaxis.
University of Zagreb, Croatia
Title: Synthesis and in vitro antitumor activity of novel 6-amidino‐substituted 2-alkyl‐bisbenzothiazoles
Time : 10:30-11:00
Livio Racané is an associate professor at the University of Zagreb Faculty of Textile technology where he teaches on undergraduate, graduate and postgraduate level of studies. He obtained his PhD in 2005. at the University of Zagreb in the field of organic chemistry. He published 30 original research articles in journals indexed in Current Contents. His main research interests are in the field of synthetic organic chemistry, medicinal chemistry and color chemistry. He was the leader of one scientific project and currently he is a collaborator on projects entitled: Exploring the antioxidative potential of benzazole scaffold in the design of novel antitumor agents financially supported by the Croatian Science Foundation under the number: HRZZ-IP-2018-01-4379.
Statement of the Problem: Classical chemotherapy, based on the use of small molecules or bioactive natural products, is still the mainstay for cancer treatment that aims at major cellular targets such as DNA, tubulin or protein kinases. Even though chemotherapy remains the standard cancer therapy option, the use of available chemotherapeutics is rather limited due to severe side effects or a limited choice of available anticancer drugs. This clearly underscores the need for development of more effective cancer treatments and new class of chemotherapeutics.
Methodology & Theoretical Orientation: Benzothiazoles and their derivatives have shown a wide range of biological activities such as anticancer, antimicrobial, antiviral and antioxidant. In continuation of our recent studies in the synthesis and evaluation of antiproliferative activities of amidino-substituted 2-aryl(heteroaryl)bisbenzothiazole derivatives, we present here the design, synthesis and structure-activity relationships of a series of dicationic 6-amidino-2-alkyl-bisbenzothiazole derivatives. The synthesis of diamidino-substituted bisbenzothiazole derivatives was performed by condensation reactions of the corresponding 5-amidino-2-aminothiophenole with dicarboxylic acid. The antiproliferative, properties of the newly prepared compounds were evaluated in vitro against four human tumor cell lines: colorectal metastatic adenocarcinoma (SW620), HepG2 (hepatocellular carcinoma), CFPAC-1 (pancreatic adenocarcinoma), HeLa (cervical carcinoma) using MTT assay. As a positive control, 5-fluorouracil was used.
Findings: In vitro anti‐proliferative screening of novel diamidino‐bisbenzothiazolyl derivatives revealed moderate to strong activity on tested cell lines, depending on the type of amidinic substituent, as well as the length of the alkyl chain.
Conclusion & Significance: Based on these results, some compounds were chosen as the leading compounds for further rationalized design of the benzothiazole skeleton.
University of Zagreb, Croatia
Title: Synthesis and antiproliferative activity of novel amino substituted tetracyclic imidazo[4,5-b]pyridine derivatives
Time : 11:00-11:30
Marijana Hranjec is a full professor where she works from 2001. She obtained her PhD in 2007 in the field of organic synthetic chemistry. She is highly experienced synthetic organic and medicinal chemists with research interests including the synthesis, spectroscopic characterization and biological activity of versatile heterocyclic derivatives. She published 50 papers indexed in Current Contents and supervised 1 doctoral dissertation, co-supervised 1 doctoral dissertation, 33 graduate and undergraduate students. In 2012, she spent some time working at the Jean-Pierre Aubert Research Centre (Lille, France). She teaches several courses at undergraduate, graduate and postgraduate studies at University of Zagreb. She was awarded with 2 prestigious awards, namely, Annual award for young scientists and artists (The society of university teachers) and The prize for organic chemistry Vladimir Prelog (Croatian Chemical Society). She was the leader of two scientific projects and currently is a collaborator on two projects.
Statement of the Problem: Due to the structural similarity of imidazo-pyridine heterocyclic system with naturally occurring purines and great therapeutic potential and significance, suchlike derivatives nowadays play an important role in medicinal chemistry and drug discovery. Imidazo-pyridine derivatives foregrounded their importance in the prevention of proper functioning of cancerous cells, diseases related to the central nervous system, inflammation, etc..,
Methodology & Theoretical Orientation: Taking into account a great biological potential and the fact that imidazo[4,5-b]pyridine scaffold is among the most privileged and important building blocks in medicinal chemistry as well as our previously published significant biological results of imidazo[4,5-b]pyridine derivatives, we have designed and synthesized novel tetracyclic derivatives as novel and potent antiproliferative agents.
Findings: The synthesis of all newly prepared compounds was conducted using conventional methods of organic synthesis and microwave assisted synthesis. Tetracyclic derivatives were substituted with chosen amino side chains which have significantly enhanced the antiproliferative activity of tetracyclic derivatives and are placed at the different position of skeleton. Additionally, the impact of the N atom position in pyridine nuclei on biological activity was studied.
Conclusion & Significance: The antiproliferative activity of regioisomers was studied against human cancer cells and non-tumour cells. As a standard drug etoposide was used and interestingly, the majority of compounds showed improvement of antiproliferative activity on HCT116 and MCF-7 cancer cells when compared to etoposide. From the obtained results it could be noticed that the position of N nitrogen in pyridine ring has strong impact on the antiproliferative activity while the type of amino substituent did not influence activity signifcantly. Thus, regioisomers 6, 7 and 9 substituted with amino substistuents at position 2 showed noticeable enhancement of activity in comparison to their counterparts 10, 11 and 13 having IC50 values from 0.3 mM to 0.9 mM against all three cancer cells.
Arab Academy for Science Technology & Maritime Transport, Egypt
Title: Synthesis of 2-arylmethylthio-4-benzyl-5-methylimidazoles as anti-metastatic drug candidates through the inhibition of STAT3-SH2 pathway
Time : 11:30-12:00
Botros Y. Beshay is a young researcher who is currently an lecturer of Medicinal Chemistry, college of pharmacy, AAST. He has started his academic career as an Organic Chemistry demonstrator at Faculty of Pharmacy, Sinai University since 2009.He has obtained his Master degree in Pharmaceutical Chemistry in May 2016, from the Faculty of Pharmacy, Suez Canal University, Egypt. He is currently a PhD candidate at faculty of Pharmacy, Alexandria University since September 2016.He graduated at Jun. 2008 from Faculty of Pharmacy, Asyut University with a general grade “excellent with honor and ranked 19th”He is interested in Drug design and discovery fields where he has Designed novel ligands with promising biological activity as anticancer, antibacterial, antifungal and anti HIV agents using different molecular modelling techniques. He has a good experience on handling with different drug design software such as Discovery Studio, SYBYL, MOE, GOLD, PYMOL and Autodock.
The intrinsic inflammatory signal transducers and activators of transcriptions (STATs) are latent cytoplasmic transcription factors that can be activated in response to signals by extracellular ligands such as cytokines, growth factors, and hormones. STAT3 is well-established as a critical molecular abnormality in the biological processes leading to cancer development. Based on the structure-based pharmacophore model constructed by poli et al , we synthesized 2-arylmethylthio-4-benzyl-5-methylimidazoles and screened them for their anticancer activity. Among the synthesized compounds, 2a and 2d showed the highest activity in suppressing cancer cells and inducing apoptosis. Also, 2a and 2d exhibited marked inhibition of STAT3 transcriptional activity than the reference compounds VS1 and Md77 with an inhibitory activity up to 89 and 82% respectively at 10 µM. We further confirmed that the phosphorylation of STAT3 which was inhibited by 2a and 2d treatment. In vitro, wound-healing and transwell-invasion assays revealed that the newly synthesized compounds 2a and 2d have strong suppressive ability on the migration and invasion of 4T1 breast cancer cells. Modeling studies strongly explain the high potency of 2a and 2d toward the STAT3-SH2 domain. Notably, the binding mode of 2a is comparable to that of phosphorylated Tyr705, since it involves the same pocket in which pTyr705 is inserted when the two STAT3 subunits are assembled in the dimer. These astonishing results clearly indicate that 2a and 2d may serve as promising lead compounds as anti-metastatic STAT3-SH2 inhibitors.
Cairo University, Egypt
Title: Synthesis and biological evaluation of novel coumarin derivatives targeting acetylcholinesterase
Time : 12:00-12:30
Haidy Hany Abdel Momen El Zoheiry affiliated with Pharmaceutical Chemistry, Faculty of Pharmacy, Cairo University, Egypt.
Acetylcholinesterase (AChE) enzyme inhibition is an important target for the management of Alzheimer disease (AD) and AChE inhibitors are the main stay drugs for its management. Coumarins are a large family of compounds, of natural and synthetic origin, that exhibit a variety of pharmacological activities, including AChE inhibition. Ensaculin, a natural coumarin derivative displayed AChE inhibitory property, is under clinical investigation for potential AD management. Thus, new series of 7-(benzyloxy)-4-substituted-2H-chromen-2-one was synthesized and evaluated as AChE inhibitors. The anticholinesterase activities of the synthesized compounds were assayed according to Ellmann’s method against freshly prepared acetylcholinesterase (AChE) from Electrophorus electricus using donepezil as the reference compound. Finally, molecular docking was performed in an attempt to understand the possible binding interactions between active compounds and amino acids present in the enzyme binding site.
Mansoura University, Egypt
Time : 13:00-13:30
Mahmoud F. Elsebai affiliated with Department of Pharmacognosy, Faculty of Pharmacy, Mansoura University, Egypt. He had published many papers in several reputed jouranls.
Infection by Hepatitis C Virus (HCV) and its subsequent complications are a major cause of mortality worldwide1. In the present study, we performed a phytochemical investigation of the water extract of the leaves of the Wild Egyptian Artichoke (WEA) (Cynara cardunculus L. var. sylvestris) and subsequently we evaluated its inhibition capacity in vitro using cell-culture derived HCV. The chemical investigation of the WEA extract resulted in the identification of six compounds: a new sesquiterpene lactone (1), in addition to the known compounds (2-6). The structural elucidation of compounds (1-6) was done by extensive spectroscopic tools such as NMR and HR-MS spectroscopy. The absolute configuration was determined by TDDFT ECD calculations and comparison with the experimental CD spectra. The quantitative determination was determined through UPLC-MS quantitation. Importantly, all compounds inhibited HCV infection; compounds 1 and 2 were the most potent among the six. The EC50 were estimated at 1.03 μM, 1.27 μM and 299 μM for compounds 1, 2 and WEA extract, respectively, by using a luciferase-carrying reporter virus2. Time-of-addition experiments revealed that compounds 1 and 2 inhibit HCV virus at a time-point during entry. Furthermore, compounds 1 and 2, apart from cell-free infection inhibited HCV cell-cell transmission, too. Finally, we showed that compounds 1 and 2 inhibited HCV particles from genotypes 1a, 1b, 2b, 3a, 4a, 5a, 6a and 7a indicating that these compounds inhibit HCV cell entry independently of viral genotype or subtype. Thus, these compounds are promising candidates for the development of new pangenotypic entry inhibitors for the HCV infection.
Menoufia university hospital, Egypt
Time : 13:30-14:00
Mohamed Abdou S. El-Tabl affiliated with Chemistry Department, Faculty of Science, Menoufia University, Shebin El-Kom, Egypt. He had published many papers in several reputed jouranls.
In recent years, various strategies have been suggested to improve the microbial resistant drugs. One of the recommended strategies has involved the combination of other molecules with the failing antibiotic drugs which apparently restores the desirable antimicrobial activity. These molecules can create opportunities for innovative therapeutic approaches. In regards to this case, paracetamol (N-(4-hydroxy phenyl) acetamide) has exhibited potent activities such as headache, muscle aches, arthritis, backache, toothache, cold and fever. It relieves pain in mild arthritis but has no effect on the underlying inflammation and swelling of the joint. New bioactive compounds N-(2-acetamido phenyl_-4-hydroxybenzamide) and its nano-organo metallic compounds have been prepared and spectroscopically characterized using 1H-NMR, Mass spectra, IR, UV-VIS and ESR spectra, Magnetic moments, Conductance measurements, as well as Elemental and Thermal analyses (DTA and TGA). In vitro antimicrobial activity of the prepared compounds was tested using the filter paper diffusion method and the chosen strains. Some of these bioactive compound exhibit very promising antibacterial and antifungal activities in comparing with standard drugs.
Energy Research Institute, UK
Time : 14:00-14:30
Abdeen Mustafa Omer (BSc, MSc, PhD) is an Associate Researcher at Occupational Health Administration, Ministry of Health and Social Welfare, Khartoum, Sudan. He has been listed in the book WHO’S WHO in the World 2005, 2006, 2007 and 2010. He has published over 300 papers in peer-reviewed journals, 200 review articles, 7 books and 150 chapters in books.
The strategy of price liberalisation and privatisation had been implemented in Sudan over the last decade, and has had a positive result on government deficit. The investment law approved recently has good statements and rules on the above strategy in particular to pharmacy regulations. Under the pressure of the new privatisation policy, the government introduced radical changes in the pharmacy regulations. To improve the effectiveness of the public pharmacy, resources should be switched towards areas of need, reducing inequalities and promoting better health conditions. Medicines are financed either through cost sharing or full private. The role of the private services is significant. A review of reform of financing medicines in Sudan is given in this article. Also, it highlights the current drug supply system in the public sector, which is currently responsibility of the Central Medical Supplies Public Corporation (CMS). In Sudan, the researchers did not identify any rigorous evaluations or quantitative studies about the impact of drug regulations on the quality of medicines and how to protect public health against counterfeit or low quality medicines, although it is practically possible. However, the regulations must be continually evaluated to ensure the public health is protected against by marketing high quality medicines rather than commercial interests, and the drug companies are held accountable for their conducts.