Day 2 :
Keynote Forum
Euis Holisotan Hakim
Institut Teknologi Bandung, Indonesia
Keynote: Bioactive natural product exploration of indonesian moraceous plants
Time : 10:00-10:30
Biography:
Euis H Hakim received a Bachelor’s degree in Chemistry from Institut Teknologi Bandung (1980) and she joined the Natural Product research group of Professor Sjamsul Arifin Achmad at ITB. She received Master’s degree (1989) and a PhD (1994) from the same university. She got a Research Fellowship at the University of Tokyo (1988), DSIR, New Zealand (1991), University of Western Australia (1992), and Post-doctoral research with Prof. Shigeo Iwasaki, the University of Tokyo (1996) and with Prof. Takeya at Tokyo University of Pharmacy & Life Science (2000). She is promoted to the position of Associate Professor in 2000 and as Full Professor in 2004.
Abstract:
About 30,000 species of plants are distributed in Indonesia and 940 species among these had been used for health care, even though only 120 species of which are involved in Indonesian natural medicines. Over the centuries, the use of medicinal plants has become an important part of daily life despite the progress in modern medical and pharmaceutical research. In connection with our continuing studies on Indonesian tropical plant, a phytochemical investigation of several families of plant has been undertaken in our laboratory, including Lauraceae, Dipterocarpaceae and Moraceae. From Lauracea family of plant, we isolated benzylisoquinoline alkaloid, 2-pyrone and lignan derivatives, while Dipterocarpaceae mostly contains stilbene oligomers. The Moraceae which is known as mulberry family comprising about 40 genera and over 1,000 species spread out in tropical and subtropical regions including Indonesia. Morus, Artocarpus and Ficus are the most important genera belonging to Moraceae family; these genera economically are valuable because of the quality of its timber and produce edible fruit. The leaves of Morus are very popular for feeding of silk worm (Bombix mori). Most of these species are used in traditional medicine in many places and well known as “sohakuhi” in Japan and “sangbaipi” in China. All parts of plant tissues of Morus alba species
are reported to be used in folk medicine (leaf for hypertension, root bark for asthma, fruit for anemia and branch for arthritis). Chemical evaluation of Artocarpus showed mainly prenylated flavonoid with variety of modified skeleton which involved pyrano-, oxepino- and xanthone- rings. And phenolic compounds isolated from Morus mostly stilbenoid and arylbenzofurane derivatives in addition to flavonoid and Diels-Alder type adducts, have exhibited an interesting biological activity including anti-tumor activity. Development of root culture of M. macroura yielded mostly Diels-Alder type adduct compounds such as Chalcomoracin and Kuwanon J, while shoots culture of this species produce a prenylated chalcones namely morachalcone and isobavachalcone which are identified as dienophile founded in Diels-Alder type adduct of Morus. The root culture of M. cathayana afforded O-methylated Diels-Alder adduct compounds which were secreted to the media. Further investigation of enzyme which is responsible for the Diels-alder adducts production of Morus plant showed a promising data for combinatorial biosynthesis study. And recently we tried to explore endophyte microbe of Morus, from which some strains of fungi containing highly potential cytotoxic cytochalasins and few compounds of epiquinophomopsin derivatives were identified.
Keynote Forum
Xiao-Ling Shen
Guangzhou University of Chinese Medicine, China
Keynote: Cajanonic acid A from Cajanus cajan regulates lipid metabolism in vitro and in vivo
Time : 10:30-11:00
Biography:
Xiao-Ling Shen PhD is a Professor at the Laboratory of Herbal Drug Discovery, Tropical Medicine Institute, Guangzhou University of Chinese Medicine. Her research focus is Chinese herbal medicines with anti-obese, anti-diabetic or anti-tumor efficacy.
Abstract:
Prevention of obesity and related lipid metabolic disorder is an important strategy in treatment and prevention of metabolic diseases such as diabetes, hyperlipidemia and hypertension. Cajanolic Acid A (CAA) is a stilbene isolated from the leaves of Cajanus cajan (L.) Mills. exhibiting PTP1B inhibitory activity in our previous screening. Activity of CAA on lipogenesis and lipolysis was also investigated. In our study, CAA inhibited the differentiation of 3T3-L1 preadipocyte into mature adipocyte, at the same time it inhibited TG accumulation within mature 3T3-L1 adiocyte and reduced the release of glycerol and Free Fatty Acids (FFA) by the cell. Further study revealed that CAA inhibits adipocyte differentiation and TG synthesis via down regulation of PPARγ and C/EBPα which are key transcriptional factors in adipocyte differentiation, and other adipogenic genes (ACC, FAS, LPL, etc.), and inhibits mature adipocyte to release glycerol and FFA by down-regulating genes related to lipolysis (HSL and ATGL), and up-regulating genes (ACOX & CPT-1) crucial to fatty acid oxidation. Ability of CAA to regulate lipid metabolism was confirmed in Zucker fatty rats, treatment with CAA achieved dose-dependent reduction in serum levels of TC and inhibition in increase of serum TG. In T2DM SD rats with hyperlipidemia, CAA not only inhibited the increase in
blood glucose, but also significantly reduced the serum levels of TG, TC and LDL-C, and showed protective effect on organ damage brought by hyperglycemia and hyperlipidemia. In summary, CAA improved lipid metabolism both in vitro and in vivo, showing potential in treatment of hyperlipidemia.
Keynote Forum
Peyman Salehi
Shahid Beheshti University, Iran
Keynote: Synthesis of novel norsufentanil analogues via a four-component Ugi reaction and in vivo, docking, and QSAR studies of their analgesic activity
Time : 11:15-11:45
Biography:
Peyman Salehi received his BSc in Chemistry in 1987 from Ferdowsi University, Mashhad, Iran. Then he moved to Shiraz University where he received his MSc in 1990 and PhD in 1995 in Organic Chemistry. He started his academic work at Razi University, Kermanshah as an Assistant Professor in 1995. After five years, he moved to Shahid Beheshti University as an Associate Professor. Since 2005, he works as a Professor in the Department of Phytochemistry. He has published more than 160 papers in peer reviewed international journals.
Abstract:
Novel pseudo peptide tethered norsufentanil derivatives were synthesized by the four-component Ugi reaction. Norsufentanil
was reacted with succinic anhydride to produce the corresponding carboxylic acid. The resulting carboxylic acid has
undergone a multicomponent reaction with different aldehydes, amines, and isocyanides to produce a library of the desired
compounds (Scheme 1). In all cases, amide bond rotation was observed in the NMR spectra. In vivo analgesic activity of
the synthesized compounds was evaluated by a tail flick test. Very encouraging results were obtained for a number of the
synthesized products. Some of the synthesized compounds such as 5a, 5b, 5h, 5j and 5r were found to be more potent than sufentanil, sufentanil citrate, and norsufentanil. Binding modes between the compounds and mu and delta opioid receptors were studied by molecular docking method. The relationship between the molecular structural features and the analgesic activity was investigated by a Quantitative Structure-Activity Relationship (QSAR) model. The results of the molecular modeling studies and the in vivo analgesic activity suggested that the majority of the synthesized compounds were more potent than sufentanil and norsufentanil.
- Agriculture Chemistry | Phytomedicine | Natural Products and Heterocyclic Chemistry | Biologically Active Natural Products and Drugs | Herbal Drugs | Advanced Synthesis and Catalysis | Medicinal Chemistry and Drug Synthesis | Bioorganic and Medicinal Chemistry | Marine Drugs
Location: Krisztina
Chair
Takashi Takahashi
Yokohama University of Pharmacy, Japan
Session Introduction
Manashi Garg
Assam Downtown University, India
Title: An in vitro comparative study on antioxidant, antibacterial and nutraceutical properties of three different coloured scented rice varieties of North- Eastern region
Time : 11:45-12:10
Biography:
Manashi Garg is a professor of Biotechnology & Biochemistry at Assam Downtown University, India. Her research focus in vitro antibacterial activity of biosynthesized silver nanoparticles from ethyl acetate extract of Hydrocotyle Sibthorpioides against multidrug resistant microbes.
Abstract:
North-East region of India is rich in production of colored and scented rice, a hulled grain with a distinctive red or purple color in addition to light grey on its bran. Of all the colored rice, especially black rice has long been consumed and is considered as a healthy food in Korea. Although, the colored rice is hard in its cooking texture, they possess beneficial effects of colored pigment, the naturally occurring colored substances like anthocyanin that belongs to flavanoids family which is reported to combat against the damaging effect of toxic free radicals and has great pharmacological property. Equally interesting is this food for the elimination of a series of other problems including obesity, edema, hypertension, diseases of kidneys and diabetes by releasing glucose in a fairly moderate way. The presence of oryzanol in the whole rice also ensures its affectivity in reducing cholesterol level (LDL) in blood. With its potent bio-active compounds such as phenolic compounds, tannins, lignin, oryzanol, tocotrienols, tocopherols, phenyl propanoids, and flavonoids, the colored rice(s) are responsible for counteracting wide range of illnesses.
Banasmita Devi
Assam Downtown University, India
Title: Extraction, isolation and characterization of Tocotrienol from glutinous black rice variety of North East India and its active nanoformulation against chronicity
Time : 12:10-12:35
Biography:
Banasmita Devi is a professor of Biotechnology & Biochemistry at Assam Downtown University, India. Her research focus in vitro antibacterial activity of biosynthesized silver nanoparticles from ethyl acetate extract of Hydrocotyle Sibthorpioides against multidrug resistant microbes.
Abstract:
The reported nutraceutical content in Chakhao, the Manipuri aromatic black glutinous rice of North East India has been reported
with great value for human health benefit. Besides these, the dietary supplement of anthocyanin rich berries has shown effective
in reducing oxidative stress, the risk of cardio vascular disease and cancer with anti-inflammatory, and also inhibits tumor cell
proliferation. The present study conducted to evaluate the antioxidant, antibacterial and nutraceutical properties of three colored
scented rice varieties grown in North Eastern region showed a significant correlation of all the rice varieties. Antioxidant activity
was measured using hydrogen peroxide and 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging assays. The antioxidant
activities of the studied samples were expressed as percentage (%) of DPPH and H2O2 radicals’ inhibition and IC50 value. Among
different extracts of crude rice, methanolic extract of the black rice showed highest antioxidant activity compared to the aqueous
extract of the other two varieties, each for DPPH (89.29±0.139) as well H2O2 (80.97±0.091) with an IC50 value of 40 μg/ml and
42.6 μg/ml respectively. Also the result of MIC against the tested Staphylococcus strain was notably found to be effective with a
significant value of 119 μg/ml for black rice taken DMSO as the positive control. In further continuation of our research, one of
the potent nutraceuticals of black rice, Tocotrienol has been extracted, isolated and characterized for its activity by formulating it
in various forms including nanocapsules. As a preliminary work of study, the active compound was evaluated against various few
prevalent pathogenic microorganisms in dermatophytic infections. The active compound was re-introduced against various infections
aided by a novel nanocapsular drug delivery system. Tocotrienol along with curcumin was encapsulated in a biodegradable polymer
(Chitosan) pluronic composite nanocapsule (TOC-Cur-CHI-P NCs) which functions exceptionally well as topical therapeutics and helped to achieve better hydrophilicity, bioavailability and controlled drug delivery with enhanced therapeutic index. The TOC-Cur- CHI- P NCs could encapsulate 98.68% of the active compounds and were found to be stable for around three months duration. The in vitro anti-bacterial activity was performed and exhibited significantly enhanced anti-chronicity activity against few isolates. With sustain release kinetics, this novel delivery system for the active compounds could bring into new point of its application. Various studies have been extended for its further application in cancer research.
Gayane Atazhanova
National Academy of Sciences of the Republic of Kazakhstan, Kazakhstan
Title: Sesquiterpene lactones from Artemisia L. endemic species
Time : 12:35-13:00
Biography:
Abstract:
Plants from Artemisia L. genus belonging to Asteraceae Dumort. family are one of the main sources of sesquiterpene lactones.
Ninety species of wormwood grow in the territory of Kazakhstan, 20 of which are endemic and considered as potential sources
of novel, previously unexplored natural compounds, especially sesquiterpene lactones. We have carried out the chemical analysis
of 11 endemic plant species from Artemisia L. genus for the first time, they are as follows: Artemisia aralensis Krasch., Artemisia
cina Berg., Artemisia filatovii A. Kuprijanov sp. nova, Artemisia glabella Kar. et Kir., Artemisia halophila Krasch., Artemisia hippolyti Butkov, Artemisia karatavica Krasch. et Abol., Artemisia radicans A. Kuprijanov sp. nova, Artemisia saissanica (Krasch.) Filat., Artemisia semiarida (Krasch. et Lavr.) Filat., Artemisia succulenta Ldb. Fl. Alt. From 11 endemic species of Artemisia L. 25 sesquiterpene lactones were determined. In doing so, 7 new sesquiterpene lactones were isolated, and the structures of their molecules elucidated by means of modern physical, chemical and spectral methods (IR-, PMR-, 13С NMR, mass-), including X-ray analysis.
Zhao Qu
Guangzhou University of Chinese Medicine, China
Title: Anti-neuroinflammatory mechanism of 7-methoxyflavanone in lipopolysaccharidestimulated BV2 microglia cells
Time : 13:35-14:00
Biography:
Zhao Qu is a post-doctoral fellow at Guangzhou University of Chinese Medicine, China. She is expertise in natural products and medicinal chemistry.
Abstract:
Microglia plays an important role in the neurodegenerative diseases in the central nervous system. Over activated microglia also leads to the production of excessive inflammatory molecules and deleterious consequences, including neuronal death. 7-methoxyflavanone (MF), one of the nature flavone extracted in Ixeridium gracile, has been shown to inhibit the cytochrome P450 aromatase and the MAO-B. However, its function and the underlying mechanisms in neuroinflammation responses in microglia remain poorly understood. In this study, we investigated MF inhibited expression of COX-2 and inflammation mediators ICAM-1 and MCP-1 in Lipopolysaccharide (LPS)-stimulated BV-2 microglia. MF also reduced the production of pro-inflammatory cytokines (TNF-α and IL-6) induced by LPS. Furthermore, investigation of the molecular mechanism indicated that MF inhibited the phosphorylation of ERK and JNK at a lower concentration than that for p38 MAPK. Further experiments revealed that MF treatment considerably increased the activation of Nrf2 and the expression of its target genes, including HO-1 and NQO1. MF also induced phosphorylation of AMPK/LKB in microglia. Interestingly, we found that MF inhibits TLR4/MyD88 signaling by interfering with LPS and TLR4 interactions. Therefore, MF might be useful as a therapeutic agent for the treatment of neuroinflammation-associated disorders such as Alzheimer's disease and Parkinson's disease.
- Pharmaceutical Sciences | Pharmaceutical Analysis | Drug Discovery and Research | Drug Therapy | Pharmaceutical Analysis | Innovations in Drug Development | Regulatory Affairs
Location: Krisztina
Chair
Minjun Chen
US Food and Drug Administration, USA
Co-Chair
Peyman Salehi
Shahid Beheshti University, Iran
Session Introduction
Gulnara Kahakimova
“NPF â€Materia Medica Holding, Russia
Title: Modern tool of pathogenetic therapy as exemplified in application of antibodies to S100 protein in the released-active form
Time : 14:00-14:25
Biography:
Gulnara Khakimova completed her Graduation from Kazan State University (Kazan, Russia) with a Master degree in Physiology. Then, she received her PhD in Neurobiology from the Koltzov Institute of Developmental Biology of Russian Academy of Sciences (Moscow, Russia). Presently, she is a Senior Researcher in
Research & Analytical Department of Russian Pharmaceutical Company Materia Medica Holding.
Abstract:
For mental disorders most commonly applied drugs are benzodiazepines and selective serotonin reuptake inhibitors. However, these drugs have a number of side effects which limit their use in ambulatory practice, especially for people whose profession requires quick mental and motor responses. Furthermore, long-term use of such drugs creates a high risk of mental and physical dependence.
Methodology & Theoretical Orientation: The alternative is to correct violations of brain integrative activity. That could be done by modulating the functions of endogenous regulatory molecules, for example, those of S100 protein. It is involved in the pathogenesis of different psychiatric disorders. S100 function can be influenced by the use of antibodies. Modulation of S100 proteins’ functions is a key mechanism of action of Tenoten® and Divaza® – drugs presented on Russian and CIS pharmaceutical markets. As the active pharmaceutical ingredient they contain antibodies to S100 in released-active form (RA anti-S100) produced by ultra-high dilution technology. It was found that these types of drugs can modify conformation of their targets and thereby change the strength of ligand-receptor interaction. Spectrum of RA anti-S100 pharmacological activity has been shown in the numerous experimental
and clinical studies.
Findings: It has been proved that RA anti-S100 have anxiolytic, antidepressant, anti-stress, anti-aggressive, nootropic (anti-amnestic,
neuroprotective) and neurotrophic activities without sedative and muscle relaxant effects and any type of dependence.
Conclusion & Significance: Treatment with drugs containing released-active forms of antibodies to S100 protein is modern tool of
pathogenetic therapy.
Jacinthe Lemay
Kuwait University, Kuwait
Title: Adverse drug reaction reporting in primary care in Kuwait: A comparative study between physicians and pharmacists
Time : 14:25-14:50
Biography:
Jacinthe Lemay joined the pharmaceutical industry in 2002 where she held different positions in the fields of clinical research, medical affairs and regulatory affairs in a wide-range of therapeutic areas. In her current position as an Assistant Professor at Kuwait University, her main research interests include optimization of healthcare delivery by working on the development and implementation of clinical pharmacy in Kuwait and developing strategies to improve medication safety and adherence to treatment.
Abstract:
Adverse Drug Reactions (ADRs) are a significant cause of morbidity and mortality. However, little is known about ADR reporting practices among Healthcare Professionals (HCPs) in Kuwait, especially in the primary healthcare setting. The objective of this study is to investigate and compare knowledge, attitude and practices regarding Pharmacovigilance (PV) and ADR reporting among physicians and pharmacists in primary care. A descriptive, cross sectional study was carried out. A validated self-administered questionnaire was distributed to a total of 583 physicians and pharmacists in 38 primary care clinics in Kuwait. Statistical analysis was done using the Statistical Package for Social Science version 23. Categorical variables were described using numbers and percentages. The Pearson chi-square or Fisher’s exact tests were used wherever appropriate. Out of 583 distributed questionnaires, 485 were completed giving a response rate of 83.2%. The study sample consisted of 318 physicians and 167 pharmacists. A total of 52.8% and 70.5% of study participants were knowledgeable about PV and ADR definitions, respectively, with pharmacists demonstrating significantly better knowledge (p<0.001). However, the majority (89.4%) was not aware of an ADR reporting system in Kuwait. Almost every participant (97.7%) thought it is necessary to report ADRs. However, significantly fewer physicians compared to pharmacists believed that ADR reporting is a professional obligation (78.0% vs. 88.0%; p=0.007). Only 27.8% had reported them, with pharmacists having reported significantly less compared to physicians (21.7% vs. 30.8%; p=0.036). The major barrier to reporting ADRs, cited by significantly more physicians was not knowing how to report (75.2% vs. 64.7%; p=0.015). Despite the positive attitudes, results indicate suboptimal knowledge and poor practices among primary care HCPs with regards to PV and ADR reporting. Targeted and practical training on ADR reporting while ensuring a robust regulatory framework may encourage a better ADR reporting culture in the primary healthcare setting in Kuwait.
Raghunandan H V
JSS University, India
Title: Importance of data integrity in pharmaceuticals
Time : 14:50-15:15
Biography:
Raghunandan H V is currently working as Professor of Pharmaceutics JSSCP and worked as Pharmacist with over 23+ years of progressive experience in pharmaceutical quality assurance, quality control, regulatory affairs, manufacturing of formulations/API’s/biologicals, contract manufacturing and pharmaceutical technical consultation (reg. affairs, product development and quality). He has good understanding of the audits and risk management in pharmaceuticals/bio pharmaceuticals, consumer health care products like OTC/OHC/nutritional health care. He is an experienced Quality Auditor and has good experience in auditing and site quality management.
Abstract:
As per USFDA, data integrity refers to the completeness, consistency and accuracy of data. Complete, consistent, and accurate data should be attributable, legible, contemporaneously recorded, original or a true copy, and accurate (ALCOA).World Health Organization (WHO) defines data integrity as the degree to which a collection of data is complete, consistent and accurate throughout the data lifecycle. The collected data should be attributable, legible, contemporaneously recorded, original or a true copy, and accurate. Assuring data integrity requires appropriate quality and risk management systems, including adherence to sound scientific principles and good documentation practices. USFDA expects data to be reliable and accurate, necessary to have flexible and risk-based strategies to prevent and detect data integrity issues, implement meaningful and effective strategies to manage their data integrity
risks. The expectation of MHRA with respect to data integrity is the governance system should be integral to the pharmaceutical quality system. Data integrity is related to many stakeholders like patients, regulators and organization. Data integrity is applied at all stages of product life cycle from discovery to distribution and applied on GXP systems, facilities, quality system, data functions and regulatory submissions. Data integrity does matter because it is necessary to establish confidence that the quality related activities are being performed effectively and regulatory decisions depends on accurate data across product lifecycle. Data integrity lapses lead to prosecution, injunction, penalty, warning letters and import alerts affecting the overall business of the organization.
Devendra Ridhurkar
Egis Pharmaceuticals PLC, Hungary
Title: Hot-Melt Extrusion: A cost effective approach leading to enhancement of bioavailability and acceleration of drug product development process via turning poorly water soluble drugs into viable therapeutics
Time : 15:15-15:40
Biography:
Devendra Ridhurkar works as a Senior Scientist at Egis Pharmaceu¬ticals PLC, Budapest, Hungary with a focus towards development of platform and other emerging technologies in innovative and complex generic formulations. Before Egis, he worked at Dr. Reddy’s Laboratories, India. He has served as a Scientist
at IPCA laboratories, Macleods Pharmaceuticals and Alkem laboratories, India. He has 11 years of experience in drug products development, using different
approaches and various technologies which include hot melt extrusion (HME), gastro-retentive drug delivery systems, and nanotechnology and cyclodextrin
complexation. He is an expert in materializing the design of experiments (DOE) and quality by design (QBD). He obtained his MPharm and PhD in Pharmaceutics from Indian Institute of Technology, Banaras Hindu University, India. He has five patents and published eight peer-reviewed papers in reputed national and international journals. He has attended and presented his research work at various national and international conferences.
Abstract:
For orally administered drugs, water solubility and permeability are the rate-limiting factors to achieve their desired concentration in systemic circulation for the pharma¬cological response. Poor water solubility of new chemical entities belonging to Biopharmaceutical Classification System (BCS) class II and IV accounts for 40 to 70% incidence of delay or failure during the drug product development process. Therefore, turning poorly water soluble drugs into viable therapeutics is the recurring and most challenging aspect of drug product developmental process facing by formulation scientist. Hence, the poor bioavailability of the drugs has intensified demand for technologies and methods in the pharmaceutical industries to overcome their traits and meet the aforesaid challenges. Development of the formulations of BCS class II and IV drugs by converting the poorly water-soluble crystalline form into a more soluble amorphous form within the polymeric blends will enhance the solubility which in turn leads to the improved bioavailability. These formulations can be developed by adopting various solid dispersion technological approaches like Hot-Melt Extrusion (HME), kneading technique, co-precipitation, co-grinding, spray-drying, lyophilization, melt agglomeration
process and supercritical fluid process. Among all these approaches, solid dispersion prepared by HME has gained popularity in the pharmaceutical industry as a means of improv¬ing the bioavailability of drugs due to its wide applications, simple pro¬cess and low cost. HME is an efficient technology for producing solid molecular dispersions with considerable advantages including the absence of solvents, few processing steps, and con¬tinuous operation over solvent-based processes such as spray drying and co-precipitation. Also, HME is one of the recommended processes by FDA to encourage move from batch-to-continuous manufacturing. Moreover, it is a value addition to intangible property of organization and can be used as non-infringing strategies for product developments.