As prior first-attempt studies revealed, ortho- or para-dihydroxyl substituents on aromatic rings could own electrochemically catalytic potentials to stimulate electron-mediating capabilities for sustainable bioenergy extraction. Follow-up serial studies pointed out that optimal supplement strategy of medicinal herbal species could effectively convert polyphenolics to be electron shuttles (ESs) for maximize bioenergy stimulation in microbial fuel cells. Evidently, several herbal species (e.g., Camellia sinensis (L.) Kuntze and Syzygium aromaticum) could be promising electroactive ES-abundant bioresources. At electrochemically-appropriate conditions, optimal contents of polyphenolics-abundant herbs and tea extracts with maximal electrochemical activities could be stably and reversibly achieved for bioenergy extraction. For example, power density of MFC supplemented with Camellia green tea extract could be significantly increased approx. 176%. Correlation analysis indicated that total polyphenolic contents, electron-shuttling capabilities and antioxidant activities were all electrochemically associated for polyphenolics-rich herbs. Although chemical structure (e.g., substitution patterns) strongly affected whether anioxidant activities of main compositions in polyphenolics-rich herbal extracts could be reversibly converted to be ES-behaved functions, toxicity potency of herbal extract might still control not only bioenergy stimulating, but also medicinal-curing potentials to be efficiently expressed. Bioelectrochemical treatment upon medicinal herbal extracts (e.g., cyclic electron-donating and withdrawing processes) might provide electroactive alternativs to attenuate such biotoxicity to efficiently exhibit bioenergy-shuttling activities for bioenergy extraction and herbal medication.
Bor-Yann Chen is Distinguished Professor of Chemical and Materials Engineering Department, NIU. He has completed PhD from University of California, Irvine USA in 1995. Prior to recruitment in 1999, he worked as NRC-awarded Research Associate in NRMRL, US EPA, Cincinnati, Ohio. He was invited to have Plenary, Keynote speeches in many International Conferences and published 150+ SCI-peer reviewed articles in reputed journals and owns many National Awards (e.g., four times Professor Yen-Ping Shih Best Paper Awards from TIChE). His research interest focued on biomass energy applications (e.g., re-evaluation of natural bioresource with electrochemical potentials for bioenergy utilization and herbal medication).
Monoterpenoid indole alkaloids (MIAs) comprise an important group of natural secondary metabolites and they are famous for their diverse structural skeletons and prominent pharmacological activities. The Pictet−Spenglerase strictosidine synthase (STR1) has been recognized as a key enzyme in the biosynthesis of some 2000 indole alkaloids in plants. Based on the observations of the X-ray crystal structure of STR1, we have tested the substrate specificity of STR1 and developed chemoenzymatic strategies to generate novel alkaloids with potential bioactivities: (i) high STR1-mediated efficient one-step preparation of tetrahydro-β-carboline alkaloids with inhibitory activities on A549 cell line. (ii) Mimicking of 3,14,18,19-Tetrahydroangustine-type alkaloid biosynthesis leading to non-Camptothecin topoisomerase I inhibitors. (iii) Sparkled rational design of unique substrate providing piperazino-indole core and pyrrole-benzazepine framework to discover non-natural alkaloids with antimalarial activity. In both cases, the (S)-configured MIAs had stronger activities than their chemically synthesized (R)-enantiomers showing the capacity and preference of bioactivities originated by STR1 from Nature. The results described here provide further insight into the biocatalytic character of STR1 and demonstrate an excellent opportunity for its use as a biocatalyst for the enantioselective construction of diversified MIAs with potentially meaningful bioactivity.
Hongbin Zou has completed his PhD from Zhejiang University, China and postdoctoral studies from Johannes Gutenberg University Mainz, Germany. He then had two years’ visiting to Bradely Moore’s lab at Scripps Institute of Oceanograph, UC San Diego, US. He is the deputy director of Institue of Drug Discovery and Design, Zhejiang University. He has published more than 30 papers in reputed journals and has authorized more than 20 patents
Pakistan, as a country with diverse agro-climatic zones, is blessed with a wide array of medicinal flora; there are enormous resources of wild plants for bioprospecting. Infact, wild plant fruits are a precious assesst of nature and offer a rich and rare pool of bioactives. The present lecture discusses the functional food and nutraceutical potential of selected wild fruits of Pakistani flora with special focus on characterization of high-value components such as phenolics, natural sugars and organic acids in the fruits of three wild medicinal plants including Olive (Olea europaea L.), Jujube (Ziziphus jujuba Mill) and Common Fig (Ficus carica L.) harvested from a unique area of Soon Valley of Pakistan. Profiling of phenolics by GC-MS-TIC method, after derivatization into silyl esters in extracts/purified fractions, showed the occurrence of different free form phenolics with trans-cinnamic and 2,4-dihydroxybenzoic acids to be the major componet in the tested fruits. After acid hydrolysis other (boound form) phenolic acids incluidng benzoic, p-hydroxybenzoic, vanillic, p-coumaric, sinapic, vanillic, p-hydroxyphenyl acetic, ferulic and sinapic acids were also detected in the tested fruits. Epicatechin was the only flavonol detected in olive fruit. HPLC analysis confirmed succinic, gluconic, and acetic acids as the major organic acids in olive, jujube and common fig fruits, respectively, however, a notable but varying amount of acetic, citric, oxalic, malic and gluconic acids were also present. Olive and jujube fruits contained galactose as dominant sugar while sucrose was a major sugar detected in common fig. These findings might be valuable towards exploring nutra-pharmaceutical potential of wild fruits from Pakistani flora.
Dr. Farooq Anwar, with PhD in Analytical Chemistry, has earned Two Post-Doc fellowships including from University of Lethbridge, Lethbridge, Alberta,Canada and Universiti Putra Malaysia, Malaysia. Presently he is serving as Professor of Analytical Chemistry, Director ORIC and Chairman of Department of Chemistry at University of Sargodha, Sargodha-Pakistan. He has supervised 12 PhD and published 223 articles with an Impact Factor > 350 and 13800 Citations to his credit. He has been enlisted as Productive Scientist of Pakistan and Fellow of the Chemical Society of Pakistan. He has been awarded Dr. Atta-ur-Rehman Gold Medal/Prize-2010 (Chemistry) by PAS and TWAS Young Affiliate Fellowship by The World Academy of Sciences (TWAS).
The efforts of our group are mainly focused on the design and synthesis of inhibitors of two enzymes groups - carbonic anhydrases (CA) and thioredoxin reductases (TrxR). Carbonic anhydrases are zinc containing enzymes which catalyze reversible hydration and transport of carbon dioxide and, along with other functions, provide pH regulation in cells. Among 15 isoforms of human CA special attention is dedicated to inhibition of tumor associated CA IX and CA XII, where good inhibitory activities and selectivities for series of bioisosteres of coumarin have been recently demonstrated. Thioredoxin reductases are selenoenzymes which are the only known enzymes to reduce Trx from its oxidized form. Since TrxR plays an important role in cellular redox balance and cancer cells are vulnerable at elevated ROS levels TrxR is an attractive drug target. In our recent studies we have found, that some of bioisosteres of coumarin effectively inhibit cancer associated TrxR1. Design and synthesis of bioisosteres of coumarin and corresponding derivatives will be discussed. Overview of their inhibition of CA, TrxR and cytotoxicity on tumor cell lines will be presented.
Prof. Raivis Zalubovskis has completed his PhD at the Royal Institute of Technology (KTH) in Stockholm under supervision of Prof. Christina Moberg. Currently he is the head of the group at the Latvian Institute of Organic Synthesis, where he also serves as the member of Scientific Board. At the same time he also holds position of associated professor at Riga Technical University. He has published more than 35 papers in reputed journals and he is a member of Editorial Board of Journal of Enzyme Inhibition and Medicinal Chemistry.
Natural products exhibit interesting biological and pharmacological activities and are currently being used as chemotherapeutic agents. Compounds that bind with microtubules are important chemotherapeutic agents for the treatment of cancer. Microtubules are built by the polymerization of α- and β- tubulin subunits. The screening of a range of botanical species and marine organisms provide satisfactory new Tubulin binding agents (TBAs). The current study targets to quantify the binding capabilities of several TBAs including vinca alkaloids, colchicine and other taxol-domain binding agents with the microtubule. In this paper molecular dynamics simulation were performed to search for the better antitubilin drugs which would be the substitute for the microtubule binding agents. The set of thirteen different molecules was selected and interacted with the microtubule. The GLIDE modules SP and XP were used for the molecular docking simulation. Docking simulations have been performed at the taxol binding site of the microtubule. The docking energy and interactions suggest that the molecule 7, 10 and 11 have a better tendency of binding with the microtubule in addition to the taxol molecule. The results of better-docked complexes have been subjected to molecular dynamics simulations for 15 ns using DESMOND. The validations of binding capabilities were checked by studying average RMSD variations and dynamical pathway observations during the course of molecular dynamics simulation. Molecular docking and molecular dynamics studies demonstrated that molecules numbered as 7(Discodermolide) and 10(Laulimalide), found to exhibit better tendency of binding with the microtubule, might be developed as a better substitute for taxol.
Prof. Umesh Yadava has completed his PhD from DDU Gorakhpur University, Gorakhpur, India and postdoctoral studies from Albert Einstein College of Medicine, New York, USA. Currently, he is working as Professor in the Department of Physics, DDU Gorakhpur University, Gorakhpur since 2016. He is the reciepient of Raman Fellowship and Young Scientist awarded by University Grants Commission, New Delhi and Department of Science and Technology, New Delhi, India respectively. He has published more than 45 papers in reputed journals and has been serving as an editorial board member of repute.
Boron neutron capture therapy (BNCT) is a non-invasive modality of treating brain tumors as well as head and neck tumors through delivery of a molecule containing 10B atoms to the tumor, which absorb a neutron under low-energy neutron irradiation to yield unstable 11B nuclei that undergo fission to yield high energy alpha particles (4He nuclei) and high energy lithium-7 (7Li) nuclei that are limited in range to 5 to9 μm, approximately the diameter of the target cell. The challenge for improving BNCT is to target tumor cells to enable selective and efficient delivery of the 10B atoms. Recognizing that matrix metalloproteinase (MMP) enzymes, especially gelatinases MMP-2 and MMP-2, as well as collagenase MMP-13, are upregulated in tumor cells, we selected to incorporate carborane clusters into scaffolds that are known to bind potently and selectively to these MMP enzymes. Diaryl ether sulfone hydroxamate MMP inhibitors have served as clinical candidates for cancer treatment, and bear a piperidine substituent that is known to project from the MMP active site into solvent when the molecules are bound to MMP enzyme, thus enabling attachment of even very large dyes for imaging of tumors. Hence we have installed boron-rich carborane clusters to the piperidines nitrogen utilizing Click chemistry for attachement of the carborane moiety. Herein we report the successful multistep synthesis of these BNCT agents and the potent MMP enzyme inhibition by these molecules as we proceed toward in vivo efficacy testing.
Daniel Becker earned his PhD at Indiana University in Bloomington, Indiana and worked in the pharmaceutical industry in Searle, Pharmacia, and then Pfizer as a Project Leader and Research Fellow in cancer, arthritis, and cardiovascular diseases. He moved from industry and joined Loyola University Chicago in 2004 where he serves as a full Professor of Chemistry performing research in synthetic organic and medicinal chemistry, especially in antibiotics and in cancer, as well as in supramolecular chemistry. He has published more than 50 scientific papers in various areas of chemistry and is an inventor on over 50 U.S. patents.
There is a need for the development of new antineoplastic and antimicrobial therapies, with higher selectivity, leading to fewer side effects than current ones. One strategy proposed is the use of bacterial or cancer cell membranes as a therapeutic target so that their basic properties are perturbed, altering the membrane potential and inhibiting the control functions on the signaling, communication or production bioenergy processes. In recent years, a promising new class of molecules targeting bacterial and cancer cells has arisen against both of the above major world health concerns. Therapeutic peptides are a novel and promising approach for the development of both antimicrobial and anti-cancer agents that could specifically target bacteria or cancer cells with lower toxicity to normal tissues, which will offer new opportunities for cancer and infection treatments. Since lipid membranes are the major target of most of these therapeutic peptides, the development of drug resistance is less likely to occur since damaging cytotoxicity can take place within minutes of peptide introduction. Traditional design and optimization studies of peptides (or peptidomimetics) are known to be expensive and time-consuming. A detailed understanding of the molecular details of the membrane permeabilization process would allow the rational design of new molecules with the same mechanism of action, but with improved activity, selectivity, and bioavailability. Recent advances in computer power and methodology, including Molecular Dynamics simulations using coarse-grained (CG) resolution or the use of GPUs, have made possible to systematically explore events that take place into ranges where direct comparison and experimental testing are starting to be feasible, realizing the synergistic potential of a combined in-silico/in-vitro approach in the characterization of the membrane destabilization process by antitumoral or antimicrobial molecules. In this talk, some recent examples of our research related to the study of different peptides and peptidomimetics acting at the membrane level will be illustrated.
Biography: Rebeca Garcia-Fandino is a young researcher recently incorporated to the CIQUS-Santiago de Compostela University through the Ramny Cajal program, working in the field of computational simulation of supramolecular systems and using cutting-edge simulation and visualization technologies. She completed her PhD at Santiago de Compostela University and postdoctoral studies in IRBB-Barcelona and Oxford University (UK). She has published more than 30 papers in reputed journals, three book chapters and she is also author of a patent and several registered software. She has been PI in several national and international competitive funded projects, and is also the main founder of the university start-up MD.USE Innovations SL.
Nyctanthes arbortristis Linn is traditionally used as anticancer herb in Indian system of medicine but its introduction into modern system of medicine is still awaited due to lack of systematic scientific studies. The objective of the present study was to isolate and characterize anticancer phytoconstituents from N.arbortristis L. leaves based on bioactivity guided fractionation. Different extracts of the leaves of the plant were prepared by Soxhlet extractor. Each extract was evaluated for anticancer activity against HL-60 cell lines. Chloroform and HA extract showed potent anticancer activity and hence were selected for fractionation. Fraction C1 from chloroform extract was found to be most potent amongst all when tested against three cell lines (HL-60, A-549 and HCT-116) and thus was selected for further fractionation and a pure compound CP-01 was isolated. RP-HPLC method has been developed for quantification of isolated compound by using Kinetex C-18 column with gradient elution at 0.7 mL/min using mobile phase containing potassium dihydrogen phosphate (0.01 M, pH 3.0) with acetonitrile. The wavelength of maximum absorption (λmax) selected was 210 nm. The structure of potent anticancer CP-01 was determined on the basis spectroscopic methods like IR, 1H-NMR, 13C-NMR& Mass spectrometry and it was characterized as 1,1,2-tris(2,4-di-tert-butylbenzene)-4,4-dimethyl-pent-1-ene. The content of CP-01 was found to be 0.88 %w/w of chloroform extract and 0.08 %w/w of N.arbortristis leaves. The study supports the traditional use of N. arbortristis as anticancer herb & the identified compound CP-01 can serve as an excellent lead to develop potent and safe anticancer drugs.
Dr. Parul Grover has completed her PhD from Punjabi University, Patiala, India. She is Assistant Professor at KIET School of Pharmacy, KIET Institute, Ghaziabad. She has published 1 patent, 2 books, 1 book chapter and have more than 20 papers in reputed journals.
Hiroshi Tomoda graduated from the University of Tokyo, Japan and obtained a PhD degree from the same. After that, he has worked for Kitasato Institute and Kitasato University. During the employment, he had an experience to work as a postdoctoral fellow at the Johns Hopkins University, USA. He became a professor of Kitasato Institute for Life Sciences, Kitasato University in 2000, then moved to Graduate School of Pharmaceutical Sciences, Kitasato University in 2005. He has discovered a number of bioactive compounds from microorganisms and published more than 300 papers in international journals. He has been serving as an editorial board member of J. Antibiotics.
Recently, many works highlighted that in Glioblastoma Multiforme, integrinsα5β1 and p53 are part of convergent pathways in the control of glioma apoptosis. Particularly, the expression profiling of high-grade glioma revealed that genes encoding for extracellular matrix components (e.g.fibronectin) and their regulators (mainly α5β1, αvβ6, αvβ8, and αvβ3)are often affected in the gliomas patients and that the simultaneous inhibition of α5β1 and αvβ3 integrins is a really successful approachto block adhesion to fibronectin in U87MG glioma cells. Also, α5β1 antagonistcan provoke cell cycle arrest, decrease cell aggressivenessand sensitize p53 wild-type (p53-wt) glioma cells to chemotherapeutic drugs. These results provide a robust rationale for a simultaneous targeting of RGD integrins and MDM proteins to increase the efficacy of anti-GBM therapeutic regimens. Here, the discovery of the first compound that inhibits both MDM2/4 and α5β1/αvβ3 integrins and its optimization is reported. Finally, the optimization process brought to life a potent MDM2/4 and α5β1/αvβ3 blocker. In p53-wild type glioma cells, this potent molecule arrested cell cycle and proliferation and strongly reduced cell invasiveness, emerging as the first molecule of a novel class of integrin/MDM inhibitors, which might be especially useful in subpopulations of patients with glioblastoma expressing a functional p53 concomitantly with a high level of α5β1 integrin.
Dr. Valeria La Pietra is Assistant Professor in Medicinal Chemistry at the University of Naples "Federico II". She got her Ph.D. in Pharmaceutical sciences in 2010after one year stint at the laboratory of Prof. William Jorgensen at Yale University (USA) pursuing research in the field of Free Energy Perturbation.In August 2017 she obtained the national scientific qualification of Associate Professor. Specifically, she is highly involved in the discovery of new chemicals especially for cancer therapy. So far, she has published more than 30 papers in reputed journals mostly working on anticancer targets: P53-MDM2/4, INTEGRINS, CXCR4 and some KINASES.
Ana Cristina Lima Leite has completed his PhD from Université de Montpellier I, France. She is a professor at University Federal of Pernambuco organization. She has published more than 55 papers in reputed journals and has been serving as an editorial board member of repute in Medicinal Chemistry field.
Among the strategies that may lead to the discovery of new drugs, the identification and use of privileged structures (PS) have gained special attention. Privileged motifs are recurring in a wide range of biologically active compounds that reach different pharmaceutical targets and pathways and could represent a suitable start point to access potential candidates in the neglected diseases field. Due the lack of financial return, only few pharmaceutical companies have been investing in research for new therapeutics for neglected diseases (ND). Drugs available to treat NDs present some issues: limited number, low efficacy, toxic side effects, and appearance of resistant strains. The PS strategy has been employed targeting T. cruzi and Zika virus. T. cruzi is a major public health problem in tropical and subtropical countries that affects approximately 6-7 million of people worldwide. Zika virus (ZIKV) is a member of the Flavivirus genus within the family Flaviviridae. ZIKV infection has already been reported in 60 countries on different continents. These two ND were used as a target by thiazoles derivatives. Thiazole nucleus are an example of a privileged molecular framework, displaying a broad spectrum of biological activities. A series of thiazole derivatives were obtained using molecular hybridation and affordable procedures. The biological assays indicated that these thiazoles present potent anti-T. cruzi and anti-ZIKV activities. They inhibited more than 90% of the ZIKV titer and exhibited IC50 values against T. cruzi similar to benznidazole (reference drug). The results prompt us that these compounds are promising anti-ZIKV and anti-T. cruzi candidates.
The antidiabetic effect of Cymbopogon citratus (lemon grass) has been demonstrated. This study evaluated the insulinotropic properties of C. citratus using gene expression. C. citratus was administered to normal rats as pulverized leaves (2%, 10% and 30%) mixed with animal feed for one week; as aqueous and ethanol extracts at a dosage of 30 and 100mg/kg for 30days; and as isolated saponins, flavonoids and tannins at 30µg/kg for 7 days. Animals were sacrificed after the treatment protocol and organs of interest removed for analysis. Gene expression analysis of C. citratus was based on polymerase chain reaction (PCR) for the bile acid TGR5 membrane receptor agonism, and GLP-1/Insulin/GluT4 gene up-regulation using isolated mRNA. Pancreas and kidneys of normal animals were queried in response to their ability to potentiate overproduction of interleukins-1 (IL-1) and tumor necrotic factor–alpha (TNF-α). Results showed that the three methods of C. citratus administration up-regulated insulin and GLP-1 gene expression in a dose-dependent manner. Following a 30-day oral treatment, the ethanol extract of C. citratus showed higher intensity ß-actin signal which was used to normalise the TNF-α and IL-1 bands, hence, ethanol extract may be said to have down-regulated the expression of TNF-α and IL-1, indicating kidney protection. The pancreas responded to ethanol extract, saponins and flavonoids of C. citratus by up-regulating GLP-1 ready for GLP-1 receptor activation and provided the insulin required for exocytosis. It can be concluded that the pharmacology of C. citratus favours its insulinotropic properties.