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Despite tremendous strides in modern medicine stringent control over insulin resistance or restoration of normoglycemia has not yet been achieved. With the growth of molecular biology, omics technologies, docking studies, and in silico pharmacology, modulators of enzymes and receptors affecting the molecular pathogenesis of the disease are being considered as the latest targets for anti-diabetic therapy. Therapeutic molecular targets are now being developed basing on the up or down regulation of different signaling pathways affecting the disease. Phytosynergistic antidiabetic therapy is in vogue both with classical and non-classical medicinal systems. However its chemoprofiling, structural and pharmacokinetic validation awaits providing recognition to such formulations for international acceptance. Translational health research with its focus on benchside product development and its sequential transition to patient bedside puts the pharma RDs to a challenge to develop bio-waiver protocols. Pharmacokinetic simulation models and establishment of in vitro-in vivo correlation can help to replace in vivo bioavailability studies and provide means of quality control for scale up and post approval modification. This EDITORIAL

Plant bioactives have a great role in combating multifactorial disease conditions like metabolic syndrome (MetS). This research work aims to develop a standardized plant extract combination and formulate it to tablets with nutraceutical potentials. The extract was prepared from the bark powder of Ficus religiosa, seed powder of Syzigium cumini and leaf powder of Ocimum bacilicum chemometrically optimized in the ratio of 1.15:1.15:1.68 (Ashwattha: Jamun: Basil or FR: SC: OB). It is enriched in screened and pharmacologically active plant secondary metabolites. The tablets were prepared by direct compression using single-punch tablet machines. The nutraceutical tablets passed all the prescribed quality control tests with a justified pharmacokinetic profile. Results of animal experimentations have shown the hypoglycemic, hypolipidemic effect and antihypertensive effect of the nutraceutical tablets in relevant animal models. Thus, the nutraceutical formulation that showed effectivity in combating MetS can be opted as an adjunct therapy.

Aim of the study is to chemometrically optimize the extraction procedure of tea polyphenolics, evaluate antioxidant potentials of fresh tea leaves and made tea grown in the non-traditional tea zone of IIT Kharagpur by in vitro assays, in silico docking studies and in vitro AChE inhibitory assays. Total tea polyphenolics, flavonoids and volatile contents of aqueous and methanolic extracts of fresh tea leaves and made tea were estimated by UV, HPLC and GC-MS analysis. The extraction process parameters were optimized by central composite design of chemometrics to maximize polyphenol yield. Antioxidant properties were studied by in vitro DPPH radical scavenging, FRAP, ABTS and Dot Blot Assay. In silico GRIP docking studies were done to evaluate the effectivity of tea catechins as antioxidants against the targeted proteins. In vitro AChE inhibitory assay was done to see its anti-Alzheimer effect. Basing on desirability function, 3.75±0.04 g of sample weight and 207.32±0.01 mL of methanol of TV fresh leaf varieties gave percent yield of poly phenols in range of 31.35 ± 2.78 -25.14 ± 1.74 and for aqueous extract the polyphenol yield range was from 21.94 ± 2.06 -20.13 ± 2.78. Both fresh leaf and made tea of TV 25 variety gave highest polyphenol yields of 31.35±2.78% (methanol) and 9.84±0.79% (aqueous) respectively. In silico GRIP docking studies showed epi-catechin gallate as the most potent antioxidant. The IC50 values for AChE inhibitory assay of black tea (CTC) was found to be 34.18µg/mL. Amongst three varieties (TV 25, TV 26 and TV 23), both fresh leaf and made tea of TV 25 variety showed maximal poly phenol content with highest antioxidant potential and were found to be comparable to Assam clones in this respect. The same fact is also reflected in the AChE inhibitory assay. Considering the significant polyphenol content and anti-oxidant capacity it can be concluded that these tea polyphenols can serve the purpose of adjuvant therapy in Alzheimer.

The application of in silico tools in the development of anti cancer drugs.

Objective: The summing of different computer aided drug design approaches that have been applied in the development of anti cancer drugs.

Method: Structure based, ligand based, hybrid protein-ligand pharmacophore methods, Homology modeling, molecular docking aids in different steps of drug discovery pipeline with considerable saving in time and expenditure. In silico tools also finds applications in the domain of cancer drug development.

Results: Structure-based pharmacophore modeling aided in the identification of PUMA inhibitors, structure based approach with high throughput screening for the development of Bcl-2 inhibitors, to derive the most relevant protein-protein interactions, anti mitotic agents; I-Kappa-B Kinase β (IKK- β) inhibitor, screening of new class of aromatase inhibitors that can be important targets in cancer therapy.

Conclusion: Application of computational methods in the design of anti cancer drugs was found to be effective.