Biography:

Concepción González-Bello has obtained her PhD at the University of Santiago de Compostela (USC, Spain) in 1994. She did two Pre-Doctoral stays in the University of Gent (Belgium) with Professor Vandewalle and in the Scripps Research Institute (USA) with Professor Nicolaou. After a Postdoctoral stay in the University of Cambridge (UK) with Professor Abell, she joined USC as an Assistant Professor, was promoted to Associate Professor in 2003 and obtained the Spanish habilitation to Full Professor in 2011. She is Author of more than 65 papers and several book chapters. She is a Member of the ChemMedChem International Advisory Board.

Abstract:

According to the World Health Organization, antibiotic resistance is becoming a public health emergency of unknown proportions. Therefore, there is a great interest in the discovery of novel drugs and therapies to tackle antimicrobial resistance, in particular drugs that target unexplored essential processes for bacterial survival. For this purpose, a detailed knowledge of the catalytic mechanism, the binding determinants and the essential motion for catalytic turnover of selected enzymes involved in biosynthetic pathways or processes that do not have mammalian homologs, but are essential for bacterial survival, can be valuable for the rational design of these mimetics (inhibitors) that can be used as drugs. Our research group is studying the possible development of new antibiotics whose mode of action is based on the selective and effective inhibition of an essential enzyme in bacteria that does not have any counterpart in human cells, shikimate kinase (SK). This enzyme is essential in relevant pathogenic bacteria such as Mycobacterium tuberculosis, Helicobacter pylori and Pseudomonas aeruginosa and catalyzes the stereospecific phosphorylation of the C3 hydroxyl group of shikimic acid by transferring the γ-phosphate group of ATP to the hydroxyl group to provide shikimate 3-phosphate and ADP. Here, we report results from NMR, biochemical, structural and molecular dynamics simulation studies that help understand the catalytic mechanism of the SK enzyme. Based on these results, several competitive inhibitors of the enzyme were designed. Our recent results on this project will be presented.

Biography:

Tatsuya TAKAGI has completed his Ph.D. at the age of 32 from Osaka University.At that time, he had been an Assistant Professor of School of Pharmaceutical Sciences, Osaka University for 5 years. Then, since 1993, he had worked for the Genome Information Research Center, Osaka University as an Associate Professor until he became a professor of Graduate School of Pharmaceutical Sciences, Osaka University in 1998. He has published more than 100 papers in reputed journals and serving as Chairman of Division of Structure-Activity Relationship of the Pharmaceutical Society of Japan.

Abstract:

Since dengue virus (DENV) infection causes epidemics in tropics/subtropics, some times it causes a potentially lethal complication, dengue hemorrhagic fever. Unfortunately, there are no effective drugs or vaccines against this infection. Thus, development of drugs and vaccines against DENV is expected. Recently, we found SK-12, a novel NS2/NS3 protease inhibitor, by structure-based in Silico screening. In this study, we carried out some ligand-based in Silico screening studies forim proving the inhibitors based on the structure of SK-12. First, we defined a pharmacophore of SK-12, and then carried out a pharmacophore search using a compound database. Next, some fingerprints of SK-12 and of compounds in the same database were obtained and then a similarity search for the compounds was carried out. As the compound database, OCDD compound library provided by the University of Tokyo was used. All these calculations were operated by MOE (CCG Inc.). Finally, 80 compounds were extracted based on the docking score obtained by MOE Dock, from the compounds obtained by the abovementioned procedure. Viral replication assays and toxicity measurements of them by MTT assay showed that EC50=0.51µMfor compound 1 (SK-12,EC50=2.55µM),which indicates that compound 1 is more active than SK-12. However, in vitro protease assay of compound 1 showed no inhibitory activities against NS2B/NS3. Then we tried to search the target molecules of compound 1, which might be the novel target molecules of anti-DENV inhibitor.(This work was supported by Project MEET, Osaka University Graduate School of Medicine, and Mitsubishi Tanabe Pharma Corporation)

Biography:

Jonathan completed his PhD at the University of York in 2005 and has held postdoctoral positions at the University of Toronto (2009) and the Australian National University (2006). Jonathan is a Senior Research Scientist at Pharmaxis Ltd in Sydney Australia where he works in the drug discovery department with roles in medicinal chemistry, computer-aided drug design and project managment.

Abstract:

Human membrane primary amine oxidase (hAOC3, also known as vascular adhesion protein-1, VAP-1) is a member of the copper dependent amine oxidase family. The enzymatic function of this protein is commonly known as Semicarbazide Sensitive Amine Oxidase (SSAO), and has been shown to play a crucial role in leukocyte rolling, adhesion and migration in various disease models. The binding site of this enzyme contains a topaquinone co-factor, derived from a modified tyrosine residue, that catalyses the oxidative deamination of primary amines to aldehydes with co-committal release ammonia and hydrogen peroxide. As part of our ongoing research into inflammatory lung diseases, we decided to target this enzyme using a mechanism-based inhibitor approach. Here we present the various challenges we have had to address during development including design, selectivity over related amine oxidases, in vitro cell health considerations and most significantly, optimisation of our molecules to be true mechanism-based inhibitors with no substrate turnover. The influence of in vitro SAR profiling and computer aided drug design will be discussed.

Biography:

Ioannis Grigoriadis has completed his PharmacistD at the age of 24 years from Aristotle University of Thessaloniki and doctoral studies from University of Ioannina Medical School. He is the scientific director of Biogenea Pharmaceuticals Ltd, a premier biotechnology personalized cancer vaccination service organization. He has published more than 25 papers in reputed journals and has been serving as an editorial board member of repute.

Abstract:

Drug discovery and development is an interdisciplinary, expensive and time-consuming process. Scientific advancements during the past two decades have changed the way pharmaceutical research generate novel bioactive molecules. Advances in computational techniques and in parallel hardware support have enabled in silico methods, and in particular structure-based drug design method, to speed up new target selection through the identification of hits to the optimization of lead compounds in the drug discovery process. Glioblastoma multiforme (GBM) is the most aggressive central nervous system (CNS) tumor because of its fast development, poor prognosis, difficult control and terrible mortality. Poor penetration and retention in the glioblastoma parenchyma were crucial challenges in GBM nanomedicine therapy. The peptide, YIGSR, decreases tumor growth and experimental metastasis via a 32/67 kD receptor. The CREKA-modified PAMAM could penetrate the GBM tissue deeply and enhance the retention effect, which was a promising strategy for brain tumor therapy Researchers have also designed and synthesized novel peptides that target a deadly brain cancer, glioblastoma multiforme, by binding to the IL-13Rα2 receptor, which is highly expressed by these cancer cells. The peptides cross the blood brain barrier and strongly bind specifically to IL-13Rα2. The peptides are conjugated to one or more drugs that are toxic to cells. Upon binding specifically to brain tumor cells, the peptide-drug conjugates are internalized and then kill the tumor cells without targeting normal brain cells. Alternatively, the peptides can deliver imaging molecules that can be used to precisely diagnose brain tumors.Identification of such sites will have use in defining strategies to develop therapeutics for cancer. Protein complexes involving IDPs are short-lived and typically involve short amino acid stretches bearing few "hot spots", thus the identification of molecules able to modulate them can produce important lead compounds: in this scenario peptides and/or peptidomimetics, deriving from structure-based, combinatorial or protein dissection approaches, can play a key role as hit compounds. Multivalency is a design principle that can convert inhibitors with low affinity to ones with high avidity and/or biological "activity" gauged by some relevant parameter: (for example, values of IC50 the concentration of free ligand, often approximated as the total ligand, that reduces the experimental signal to 50% of its initial value). In addition, multivalent approaches can be effective in generating high-avidity ligands for proteins with multiple binding sites from low-affinity ligands. Multivalent ligands (primarily polyvalent ones) are especially well suited for inhibiting or augmenting interactions at biological surfaces (e. g., surfaces of bacteria, viruses, cells they can prevent adhesion of these surfaces to other surfaces by grafting polymers to the surfaces of viruses to prevent adhesion to cells). Computational docking, colchicine-tubulin competitive binding, and tubulin polymerization studies demonstrated that these compounds bind at the colchicine-binding site on tubulin and inhibit the formation of microtubules. The mode of action of the VDAC-1 peptides involves dysfunction of mitochondria energy production and apoptosis induction. In this study, we confine attention to the so called ligand-based target prediction machine learning peptide mimetic drug discovery approaches, commonly referred to as drug target fishing. Here, in Biogenea we have for the first time discovered an in silico high binding free energy affinity value predicted Novel Hyper-Multi-Targeted computer-aided Inhibitor against tumor growth and experimental metastasis related Glioblastoma conserved motif-like peptide domains.These results demonstrate that the VDAC1 treating CLL peptides may assist target-fishing approaches that are currently ubiquitous in cheminformatics and can be essentially viewed as single-label peptidomimetic drug discovery schemes. Here, we have for the first time in silico Development of a novel class of hyper-multi-targeted computer-aided CREKA/YIGSR-peptide mimotopic dual Inhibitor against tumor growth, metastasis related glioblastoma conserved motif-like peptide domains VDAC1-peptide mimetic tubulin targeted HA14-1-based multivalent chemical inhibitorory promising anticancer activities as novel in silico high binding free energy affinity value pro-apoptotic annotated agent for B-cell chronic lymphocytic leukemia.

Biography:

Paulo Paixão has a PhD in pharmacokinetics by the University of Lisbon, is an Invited Assistant Professor on Biopharmaceuticals and Pharmacokinetics at Lisbon University and a Pharmacokinetic Assessor at the Portuguese Regulatory Agency (INFARMED.PT). He focuses his research on the development and application of modelling and simulation tools for the prediction and characterization of the pharmacokinetic properties of new molecular entities and on bioequivalence issues by using QSAR and PBPK models.

Abstract:

Purpose To develop a QSAR model, based on calculated molecular descriptors and an Artificial Neural Networks Ensemble (ANNE), for the estimation of plasma protein binding (as fraction of unbound drug in plasma - fup) of drugs in human, rat, dog and monkey plasma, as well as the assessment of the applicability domain (AD) of the model. Methods A total of 680 individual fup values (75% train and 25% validation), were collected in the literature from human, rat, dog and monkey plasma concentrations. A correlation between simple molecular descriptors for lipophilicity, ionization, size and hydrogen bonding capacity and fup data was attempted by using an ANNE. Results A degradation of the correlations was observed for predicted values with high uncertainty, as judged by the standard deviations of the ANNE outputs. Based on this, a “cut-off” SD<0.0857 was establish to consider that a particular drug is inside the AD of the model. Similar statistics were observed between the train and validation group of data, when inside the AD, with correlations between the observed values and the predicted average ANNE values, of 0.951 and 0.854, respectively. 82% of the drugs were well predicted with diference of less than 0.2 in the validation group of data, again when inside the AD (93% in the train dataset). Conclusions This model may be a valuable tool for simulation and prediction in early drug development, allowing the insilico estimation of fup in different pre-clinical models and in the human, that may be used for PBPK purposes.

Biography:

Wafi Siala is a researcher in Université catholique de Louvain, Belgium

Abstract:

Objective: Staphylococcal biofilms are poorly responsive to antibiotics. In a preliminary screening of combinations of moxifloxacin (MXF) with drugs selected based on their amphiphilic character, we observed that the antifungal caspofungin (CAS)was synergistic. Our aim was now to test this combination on biofilms preformed on catheters in vitro and in vivo. Methods: Biofilms were grown inside 1cm polyurethane catheters at 37°C for 24h (initial inoculum: 5.106 cells/ml).In vitro, 7 clinical isolates and the bioluminescent Xen36 strain were used. Biofilms grown on catheters were placed in 24-well plates, incubated with MXF(10mg/L); CAS(80mg/L) or MXF/CAS for 48 h. Catheters were washed, sonicated, and CFUs/catheter were counted.Invivo,5 catheters infected with Xen36 biofilm were implanted subcutaneously in the back of mice. Animals were treated intravenously with MXF(40 mg/kg twice daily), CAS(4 mg/kg/day) or with MXF/CAS combination during 7 days. CFUs/catheter were counted.

Results: In vitro, MXF or CAS alone caused no significant decrease in CFU/catheterfor all tested strains. When combined with CAS, MXF markedly decreased CFU/catheter in all strains, but to different extents (ranging from 2 to 8.2 log CFU decrease). Invivodrugs alone were ineffective as well. The MXF/CAS combination caused a 2.1 log CFU reduction for Xen36 (vs. 3.3 log CFU reduction against the same strain in vitro). Conclusion: CombiningMXF with CASproves highly synergistic in vitro and in vivo against staphylococcal biofilms. This will open perspective to use CAS as adjuvant for the treatment of S.aureus biofilms Log CFU/catheter Strains (origin) In vitro model Untreated MXF CAS MXF-CAS 2011/S027 (cellulitis and bacteremia) 9.08±0.98 8.82±0.24 9.14±0.17 1.43±0.36a 2003/1083 (chirurgical wound) 11.7±0.32 11.5±0.14 12.3±0.21 3.41±0.09a 2005/104 (skin) 6.87±0.32 6.51±0.44 6.99±0.22 3.01±0.32a 2009/S028 (nasal carriage) 6.88±0.22 6.45±0.12 6.78±0.09 2.70±0.15a 2009/S025 (ear) 8.12±0.44 8.16±0.99 8.47±0.45 3.55±0.14a 2005/179 (skin) 6.73±0.65 6.55±0.11 6.77±0.12 2.69±0.06a 2003/651 (respiratory infection) 5.44±0.82 4.19±0.15 5.47±0.08 3.57±0.07 a XEN36 (bioluminescent derived from S.aureus ATCC 49525) 6.26±0.22 6.23±0.32 6.35±0.14 2.91±0.65a In vivo model XEN36 7.31±0.45 6.17±0.13 7.35±0.42 5.15±0.15 b statistical analysis :comparison between MXF treated group and MXF-CAS treated group for each strain ain vitro data; P value ≤0.01 for all strains bin vivo data; P value =0.028

Biography:

Ioannis Grigoriadis has completed his PharmacistD at the age of 24 years from Aristotle University of Thessaloniki and doctoral studies from University of Ioannina Medical School. He is the scientific director of Biogenea Pharmaceuticals Ltd, a premier biotechnology personalized cancer vaccination service organization. He has published more than 25 papers in reputed journals and has been serving as an editorial board member of repute.

Abstract:

Drug discovery and development is an interdisciplinary, expensive and time-consuming process. Scientific advancements during the past two decades have changed the way pharmaceutical research generate novel bioactive molecules. Advances in computational techniques and in parallel hardware support have enabled in silico methods, and in particular structure-based drug design method, to speed up new target selection through the identification of hits to the optimization of lead compounds in the drug discovery process. Glioblastoma multiforme (GBM) is the most aggressive central nervous system (CNS) tumor because of its fast development, poor prognosis, difficult control and terrible mortality. Poor penetration and retention in the glioblastoma parenchyma were crucial challenges in GBM nanomedicine therapy. The peptide, YIGSR, decreases tumor growth and experimental metastasis via a 32/67 kD receptor. The CREKA-modified PAMAM could penetrate the GBM tissue deeply and enhance the retention effect, which was a promising strategy for brain tumor therapy Researchers have also designed and synthesized novel peptides that target a deadly brain cancer, glioblastoma multiforme, by binding to the IL-13Rα2 receptor, which is highly expressed by these cancer cells. The peptides cross the blood brain barrier and strongly bind specifically to IL-13Rα2. The peptides are conjugated to one or more drugs that are toxic to cells. Upon binding specifically to brain tumor cells, the peptide-drug conjugates are internalized and then kill the tumor cells without targeting normal brain cells. Alternatively, the peptides can deliver imaging molecules that can be used to precisely diagnose brain tumors. Identification of such sites will have use in defining strategies to develop therapeutics for cancer. Protein complexes involving IDPs are short-lived and typically involve short amino acid stretches bearing few "hot spots", thus the identification of molecules able to modulate them can produce important lead compounds: in this scenario peptides and/or peptidomimetics, deriving from structure-based, combinatorial or protein dissection approaches, can play a key role as hit compounds. Multivalency is a design principle that can convert inhibitors with low affinity to ones with high avidity and/or biological "activity" gauged by some relevant parameter: (for example, values of IC50 the concentration of free ligand, often approximated as the total ligand, that reduces the experimental signal to 50% of its initial value). In addition, multivalent approaches can be effective in generating high-avidity ligands for proteins with multiple binding sites from low-affinity ligands. Multivalent ligands (primarily polyvalent ones) are especially well suited for inhibiting or augmenting interactions at biological surfaces (e. g., surfaces of bacteria, viruses, cells they can prevent adhesion of these surfaces to other surfaces by grafting polymers to the surfaces of viruses to prevent adhesion to cells). Computational docking, colchicine-tubulin competitive binding, and tubulin polymerization studies demonstrated that these compounds bind at the colchicine-binding site on tubulin and inhibit the formation of microtubules. The mode of action of the VDAC-1 peptides involves dysfunction of mitochondria energy production and apoptosis induction. In this study, we confine attention to the so called ligand-based target prediction machine learning peptide mimetic drug discovery approaches, commonly referred to as drug target fishing. Here, in Biogenea we have for the first time discovered an in silico high binding free energy affinity value predicted Novel Hyper-Multi-Targeted computer-aided Inhibitor against tumor growth and experimental metastasis related Glioblastoma conserved motif-like peptide domains. These results demonstrate that the VDAC1 treating CLL peptides may assist target-fishing approaches that are currently ubiquitous in cheminformatics and can be essentially viewed as single-label peptidomimetic drug discovery schemes. Here, we have for the first time in silico Development of a novel class of hyper-multi-targeted computer-aided CREKA/YIGSR-peptide mimotopic dual Inhibitor against tumor growth, metastasis related glioblastoma conserved motif-like peptide domains VDAC1-peptide mimetic tubulin targeted HA14-1-based multivalent chemical inhibitorory promising anticancer activities as novel in silico high binding free energy affinity value pro-apoptotic annotated agent for B-cell chronic lymphocytic leukemia.

Biography:

Luis Manzano is a chemist laboratory technician. His work in the biochemistry laboratory at Escuela Superior de Medicina is to synthesize several compounds derivatives of phenylethylamine and perform the characterization of these molecules. Currently, he is at the first semester in biochemical engineering atEscuela Nacional de CienciasBiologicas ofInstitutoPolitecnico Nacional.

Abstract:

The Cyclooxygenase-II (COX-II) is a protein encoded by the human gene PTGS2 present in inflammatory processes. The role of COX-II is to mediate inflammation processes and prostaglandin biosynthesis from arachidonic acid. No steroidal anti-inflammatory drugs (NSAIDs) are the most frequently prescribed for the treatment of acute or chronic inflammation and offer symptomatic pain relief by inhibiting the COX-II. Most NSAIDs currently used in clinic are known to inhibit both isoforms of Prostaglandins H synthase (PGHS) with little selectivity, and during extended therapy many NSAIDs cause ulcerogenic side effects most likely due to PGHS-1 inhibition in the stomach. The structural observations in regard to the pharmacological effect of phthalimides promoted our interest to synthesize a novel series of dioxoisoindoline and investigating the anti-inflammatory activity of these compounds to COX-2 enzymes through in silico studies. We performed the molecular approach (docking) of 29 dioxoisoindolines derived of primary amines. The results showed that the best ligands were the molecules Do15-1, Do15-16 and Do15-17S with a ΔG of -8.24, -9.46 and -8.17 Kcal/mol respectively, showing a high affinity to interact with Cyclooxygenase-II. Therefore, those 3 ligands were synthesized with a green synthesis technique and their structures were confirmed by infrared spectroscopy, nuclear magnetic resonance and mass spectroscopy. In addition to the insilico results we plan to perform in vivo experiments with Sprague Dawley rats and BALB/c mice with our synthesized compounds, in order to test their possible inhibitory activity toward COX-II and their possible effects on the gastric mucosa.

Biography:

Barbara Susana Gregori Vlades is student of PhD in University o Lisbon , Pharmacy Faculty. She integrates the Nanomedicine and Drug Delivery Systems (nanoDDS) group of the Research Institute for Medicines and Pharmaceutical Sciences (iMed. FFUL), and collaborates with other research teams from Instituto Superior Tecnico and IFAL, University of Havana. She has published several papers in journals and has been serving as an editorial board member of repute

Abstract:

This study focused on the synthesis and characterization of a polyurethanes to prepare a nail lacquer formulation with terbinafine hydrochloride in order to obtain a topical nail release system The synthesis of polymer was carried out by the reaction of of IPDI, PPG and isosorbide with 6:1:5 ratio, under a nitrogen atmosphere using 0.5 mL of DABCO as catalyst. The polymer was characterized by FTIR, NMR, DSC PALS and the biocompatibility with keratinocytes cell was study.The in vitro release profile of terbinafine from diferent nail lacquer formulatios was investigated using Franz Cells. The FTIR spectrum showed a band at 1695 cm-1 attributed to the stretching vibration of the C=O carbonyl of urethane. The PU melting temperature was around 60 oC. The presence of -NH protons at 5.2 and 7.5 ppm in the 1H NMR spectrum in dmso confirm the reaction between the isosorbide hydroxyl groups and the pre-polymer isocyanate groups. The PU presents cell viability measured by the MTT reduction. The release profile, demonstrated that the formulation had the ability to release the drug. In this research new polyurethane was synthesized and characterized. The polyurethane synthesized presented biocompatibility. The results so far obtained are promising for a novel terbinafine based nail lacquer for the treatment of fungal infections

Biography:

Hafiz Ansar Rasul Suleria is a researcher in The University of Queensland, Australia

Abstract:

Marine organisms are increasingly being investigated as sources of bioactive molecules with therapeutic applications as nutraceuticals and pharmaceuticals. Recent trends in functional foods have demonstrated that bioactive molecules play a major therapeutic role in human disease, therefore nutritionists, biomedical scientists and food scientists are working together to discover new bioactive molecules that have increased potency and therapeutic benefits. Marine life constitutes almost 80% of the world biota with thousands of bioactive compounds and secondary metabolites derived from marine invertebrates such as tunicates, sponges, mollusks, sea hares, bryozoans, sea slugs and other marine organisms. These bioactives and secondary metabolites possess antibiotic, anti-parasitic, anti-viral, anti-inflammatory, anti-fibrotic and anti-cancer activities. They are inhibitors or activators of critical enzymes, agonists or inhibitors of transcription factors, competitors of transporters and sequestrants to modulate various physiological pathways. The current review summarises the widely available marine-based nutraceuticals and recent findings, mainly focusing on mode of action, efficacy and underlying mechanisms. It also presents recent research involving the isolation, identification and characterization of marine-derived bioactives with various therapeutic potentials.

Biography:

Yue-Wei Guo is a is a researcher in Chinese Academy of Sciences, China

Abstract:

Mangroves comprise a large number of various salt-tolerant plants growing in tropical and subtropical intertidal estuarine zones. Historically, many mangrove plants were used to treat various diseases in traditional Chinese medicine. Currently, the secondary metabolites found in Mangroves represent an extremely rich source of novel chemical diversity for academic drug discovery and chemical biology programs. It is particularly true that the mangroves from Southern Coast of China are very prolific producers of bioactive natural products.1 Our group at SIMM has long been engaged in the searching for novel secondary metabolites with pharmacological potential from Chinese mangrove medicinal plants.2 In collaboration with biologists and pharmacologists at SIMM, many mangroves used as fork medicine were chemically investigated and numerous novel isolates obtained were pharmacologically screened for activity in a variety of cell-based and pure enzyme assays designed to identify promising lead compounds for the development of drugs in the therapy of human diseases.3 This presentation will discuss examples of bioactive metabolites (structures and activities) from our recent discovery efforts.

Biography:

Yue-Wei Guo has completed his PhD at the age of 39 years from Naples University, Italy and postdoctoral studies from Istituto di Chimica Biomoleculare-CNR, Italy and Hokkaido University School of Pharmacy, Japan. He is the principal investigator of marine natural products Lab in SIMM, a premier drug R & D organization in China. He has published more than 320 papers in reputed journals and serving as an editorial board member of repute.

Abstract:

The steroids found in Hainan benthic marine invertebrates represent an extremely rich source of novel chemical diversity for academic drug discovery and chemical biology programs. It is particularly true that the benthic invertebrates, such as sponges, soft corals, from southern coast of China are very prolific producers of bioactive steroid natural products. Our group at SIMM-CAS has long been engaged in the searching for novel secondary metabolites, including steroids, with pharmacological potential from Chinese marine animals. In collaboration with biologists and pharmacologists at SIMM, many marine invertebrates were chemically investigated and numerous novel isolates obtained were pharmacologically screened for activity in a variety of cell-based and pure enzyme assays designed to identify promising lead compounds for the development of drugs in the therapy of human diseases. This presentation will discuss examples of biologically active and structurally interesting steroids from our recent discovery efforts

Biography:

Akbar Hedayatizadeh-Omran is a researcher in University of Medical Sciences, Iran

Abstract:

Several diseases are associated with oxidative stress caused by free radicals and reactive oxygen species. In this study, antioxidant activity of captopril was studied using in vitro assays systems. Free radical scavenging and reducing power were determined with diphenyl picryl hydrazyl free radical (DPPH method) and potassium ferricyanide method, respectively. The results of this study showed that captopril possessed a significant free radical scavenging and reducing power properties and there were a clear correlation exists between antioxidant activity and concentration of captopril. Percentage of free radical scavenging of captopril was more than 92 % at concentration 0.08 mM

Biography:

I am Sara Nasrollahi, I am graduated from master of science in applied chemistry at age of 25 from Islamic Azad University Central Tehran Branch, Tehran, Iran. I have published two papers in well-known journals about drug delivery and one paper about environmental chemistry. I also have studied on adsorbing heavy metals from environmental water samples and biological solution, and written some papers which are under revision.

Abstract:

A novel method is reported for grafting of poly [N-isopropylacrylamide-co-allylglycidyl/iminodiacetic] based on iron oxide nano-particles modified by 3-mercaptopropyltrimethoxysilane. The grafted nano-polymer was characterized by elemental analysis, Fourier transform infrared spectroscopy, thermogravimetric analysis, transmission electron microscopy and scanning electron microscopy. The analytical parameters such as pH, temperature and contact time of the grafted nano-polymer were studied. Determination and extraction of famotidine in human biological fluids were evaluated with high great accessibility to the active sites in the grafted sorbent. The equilibrium adsorption data of famotidine by grafted nano-sorbent were analyzed by Langmuir and Freundlich models. The sorption capacity of the nano-sorbent was 116 mg g-1 at an optimum pH of 7. Almost 73% of famotidine was released in simulated gastric fluid in 1 h and 70% was released in simulated intestinal fluids in 30 h at 37ËšC. These results show that this new magnetic grafted nano-polymer is adequate for enteric drug delivery. The suitable cause for choosing this particular polymer was its strong retention and subsequently longer controlled release for drug delivery. In other investigation, the effect of temperature on famotidine release was evaluated. The sorption and desorption studies were carried out at five temperatures (25-45°C). The results showed that the maximum adsorption of famotidine occurred at 30°C. Because, at low temperatures, the repeating chains of N-isopropylacrylamide on the nano-sorbent were in expanded form and famotidine better loaded onto the sorbent. At high temperature the grafted polymer containing the thermo-sensitive monomer shrank, so the release of famotidine increased.

Biography:

Kian Navaee has completed his M.Sc in organic chemistry at the age of 28 years from Institute for Advanced Studies in Basic Sciences (IASBS) in Iran. He is supervisor in research and development Department of Shahre Daru Pharmaceutical Co. in Iran. His scientific research articles cited more than 225 papers in ISI journals to present. He is full member of the American Chemical Society (ACS).

Abstract:

Artificial neural networks (ANNs) technology models the pattern recognition capabilities of the neural networks of the brain. Similarly to a single neuron in the brain, artificial neuron unit receives inputs from many external sources, processes them, and makes decisions. Interestingly, ANN simulates the biological nervous system and draws on analogues of adaptive biological neurons. ANNs do not require rigidly structured experimental designs and can map functions using historical or incomplete data, which makes them a powerful tool for simulation of various non-linear systems. ANNs have many applications in various fields, including engineering, psychology, medicinal chemistry and pharmaceutical research. Because of their capacity for making predictions, pattern recognition, and modeling, ANNs have been very useful in many aspects of pharmaceutical research including modeling of the brain neural network, analytical data analysis, drug modeling, protein structure and function, dosage optimization and manufacturing, pharmacokinetics and pharmacodynamics modeling, and in vitro in vivo correlations. These presentations will discuss the applications of ANNs in drug delivery and pharmacological research.

Biography:

Bin Xu received his Ph.D. from Case Western Reserve University in 2004; and followed by postdoctoralstudies at Fred Hutchinson Cancer Research Center. Since 2011, he has beena tenure-track Assistant Professor in the Department of Biochemistry and Center for Drug Discovery at Virginia Tech. His research interests concern cell surface receptor-ligand binding, receptor signaling, novel ligand and receptor discovery, and translational structure-based and computer-aided ligand design with applications to novel peptide hormones and natural products relevant to diabetes, obesity,neurodegenerative diseases, and nanomedicine. He has published more than two dozens publications in premier international peer-reviewed journals.

Abstract:

The incidence of type 1 diabetes (T1D) is increasing fast worldwide and currently there is no known cure for this disease. Past studies provided encouraging evidence that b-cells have the potential to regenerate primarily by proliferation of existing b-cells. Through performing a systematic screen of a natural products collection, we discovered that oleuropein, a natural compound typically found in olive leaf and fruit and olive oil, induces b-cell growth and potentiates glucose stimulated insulin secretion. Oleuropein is shown to stimulate INS1 b-cell proliferation following a 24 hour incubation period as determined by bromo-deoxyuridine (BrdU) DNA incorporation-based cell replication assay and tetrazolium MTT-based cell proliferation assay. The effect of oleuropein on β-cell growth is as potent as that of glucagon-like peptide, a known FDA-approved type 2diabetes drug. To determine the molecular mechanisms by which oleuropein induces b-cell growth and exerts its potential anti-diabetes effects, we have performed detailed signaling analyses. Our results show that oleuropein acutely (within the time-frame of 20 minutes of treatment) activated ERK1/2 in INS1 cells. Using pharmacological inhibitors, we found PD98059, a known MEK1/2 inhibitor, strongly diminished ERK phosphorylation induced by oleuropein. To further map pathways upstream of ERK-MEK, we applied a panel of inhibitors. We found small compound Sorafenib (BAY 43-9006), a kinase Raf inhibitor, significantly inhibits oleuropein-induced ERK phosphorylation. Treatments of PKA inhibitors KT5720 or H89, PI3K inhibitor LY294002, AMPK inhibitor compound C each had no significant effects. We conclude oleuropein promotes b-cell proliferation through ERK-MEK-Raf pathway.

Biography:

Olalude C.B is a researcher in The polytechnic Ibadan, Nigeria

Abstract:

Daucus Carota popularly known as Carrot is one of the most popular Root Vegetables grown throughout the World and it is one of the most important Carotenoids. Carrots are credited with many medicinal properties, they are said to cleanse the intestines and to be Diuretic, Revitalizing, Antidiarrheal, Antianemic and rich in alkaline Elements which purify and Revitalize the Blood. It also has a Repution as a Vegetable that helps to maintain good eyesight. The results of the Physicochemical Analysis of Carrot Juice was analyzed and this result showed that the moisture content is 91.000 ± 0.265 which indicates that carrot contained much water which will help in healthy hydration of the body system, in transport of nutrient, elimination of waste and body temperature regulation .protein % 1.067 ± 0.058, which indicates that carrot will serve as a collagen for supportive tissue, Heamoglobin for transport, antibodies for immune defense and enzymes for metabolism in the body and can serve as balanced diet in humans. ether extract ( crude fat) % 0.367 ± 0.089 this shows that carrot is not rich in oil i.e. does not contain much oil, ash % 1.333 ± 0.153 this means that carrot contains essential nutrient elements, as this will normally show up in the ash content of a vegetable matter and can be used to argument minerals in food formulation. crude fibre % 1.167 ± 0.153 crude fibre is desirable in meals, as they serve as digestion aids, carbohydrate % 6.100 ± 0.346 this indicate that carrot can be used as food supplement sources of carbohydrate or energy, specific gravity 1.069 ± 0.003,pH 6.333 ± 0.058,ascorbic acid 16.667 ± 1.332, Ca++ (mg/100g) 55.000 ± 0.000, Fe++( mg/100g)1.667 ± 0.153, PO4—( mg/100g)44.333 ± 1.155, thiamine (mg/100g) 0.057 ± 0.006, niacin(mg/100g) 0.300 ± 0.000, riboflavin 0.100 ± 0.000,β-carotene 2730 ± 43.589,colour (out of 10) 2.000 ± 0.000 and vitamin A 2805 ± 6.532. The results shown that vitamin A and β carotene has high content in carrot juice. As a result of these findings, carrot is save for consumption without passing any negative or deleting effect to its consumer, consumption of it should be encourage because of its health benefits.

Biography:

Currently, I am working as Assistant Professor at the Department of Biochemistry, University of Karachi, earlier completed by PhD from King’s College London, UK in 2011 in the field of Computational Biophysics. My field of specialization is “Computer Aided Drug Design”, which I teach at graduate and postgraduate level. I have supervised more than 10 Master’s thesis and also published more than 12 research articles in various scientific journals.

Abstract:

Data on phytochemical constituents of herbs commonly used in traditional Indonesian medicine have been compiled as a database using ChemDBSoft software. This database (the Indonesian Herbal constituents database, IHD) contains details on 1,242 compounds found in 33 different plants. For each entry, the IHD gives details of chemical structure, trivial and systematic name, CAS registry number, pharmacology (where known), toxicology (LD50), botanical species, the part(s) of the plant(s) where the compounds are found, typical dosage(s) and reference(s). A second database has been also been compiled for plant-derived compounds with known activity against the enzyme, aldose reductase (AR). This database (the aldose reductase inhibitors database, ARID) contains the same details as the IHD, and currently comprises information on 112 different AR inhibitors. In the search for novel leads active against AR to provide for new forms of symptomatic relief in diabetic patients – virtual screening of all compounds in the IHD has been performed using (a) random forest (RF) modelling, and (b) molecular docking. For the RF modelling, 3 sets of chemical descriptors – Constitutional, RDF and 3DMoRSE (computed using the DRAGON software) were employed to classify all compounds in the combined ARID and IHD databases as either active or inactive as AR inhibitors. The resulting RF models (which give misclassification rates of ~10%) were used to identify putative new AR inhibitors in the IHD, with such compounds being identified as those giving a mean RF score > 0.5. Virtual screening of the IHD was also performed using the docking software, Molegro Virtual Dokcer (MVD), In the docking studies reported here, carboxyl-containing IHD compounds were docked in to the active site of the 11 crystal structures of AR bound to different carboxyl containing ligands. Calculation of the averages of these 11 MVD re-rank scores was carried out as a means to identify anomalous docking results. In-vitro assays were subsequently performed to determine the inhibitory activity against human recombinant AR for four of the compounds obtained as hits in RF in-silico screenings and for a further four compounds obtained as hits in the docking studies. All four of the RF and docking hits were (as predicted) active as AR inhibitors with IC50s in the micromolar range.

Biography:

Dr. Sumeet Dwivedi has obtained his B.Pharm from Smriti College of Pharmaceutical Sciences, Indore, M.P., M.Pharm (Pharmacognosy), with Hons./Gold Medal from Vinayaka Missions University, Salem, T.N., Pursuing Ph.D. from Suresh Gyan Vihar University, Jaipur, R.J., presently working as Associate Professor and Head of the Department, Chordia Institute of Pharmacy, Indore, M.P. He is involved in research on screening, formulation, standardization of herbals, cultivation practices of medicinal plants, biotechnological approaches of herbs. He has his credit of more than 150 research/review papers in various national and international Journal of repute, has more than 50 Abstract in various Conferences, published 6 books and serving as Executive Editor, International Journal of Pharmacy and Life Sciences and Managing Editor, International Journal of Drug Discovery and Herbal Research, Reviewer of many Journals and Editorial Board Member of various Journal.

Abstract:

India is one of the richest reservoirs of biological diversity in the world. It is home to a great variety of ethno-medicinally important plant species, and is ranked 6th (sixth) among 12 mega diversity countries of the world. However, several factors are putting India’s medicinal plants at risk of extinction: the increasing demand for herbal raw-material & products, the reliance of pharmaceutical companies on plants for drugs, the encroachment of civilization into plant habitat (including timber and mining operations, shopping malls and housing developments), and the innate sensitivity or rareness of certain species. The problems are compounded by market-demand driven harvesting without any concern for representation and conservation. In the process essential regenerative components of a plant like roots, tubers, fruits, seeds, flowers and bark are indiscriminately collected, leading to degradation and depletion and even extinction of particular species. Due to this ruthless exploitation, many important medicinal plants species are becoming rare and some of them are critically endangered. The present paper deals with the need of several standardization parameters of some endangered medicinal plants of Central India. Several validation parameters such as LOD, FOM, TA, SI, HPTLC fingerprint etc were highlighted in the present communications.