Dr. S. Sathianarayanan

Abstract Tunable pH and redox responsive polymer was prepared using γ-polyglutamic acid (γ-PGA) with linker 3-mercaptopropionic acid (3-MPA) (γ-PGA_SH) via oxidation to obtain redox responsive disulfide (γ-PGA_SS) backbone and adipic acid dihydrazide (ADH) (γ-PGA_SS_ADH) with hydrazide functional group for pH responsiveness. Further curcumin (Cur) was conjugated through hydrazone bond of the γ-PGA_SS_ADH via Schiff base reaction to obtain (γ-PGA_SS_ADH_Cur). The prepared systems were characterized by Fourier transform infrared spectroscopy (FTIR), Raman spectroscopy, Electrospray ionization quadrupole time-of-flight mass spectrometry (ESI-Qq-TOF-MS/MS) and Solid state nuclear magnetic resonance (SS NMR) techniques. γ-PGA_SS_ADH_Cur formed self-assembled core shell nanoparticles (NPs) in existence of stabilized aqueous medium. γ-PGA_SS_ADH_Cur NPs maintained its stability in physiological condition. NPs tunable Cur release and cytotoxicity were observed for γ-PGA_SS_ADH_Cur NPs in both acidic and redox conditions mimicking the cancer microenvironment. γ-PGA_SS_ADH_Cur NPs uptake study showed via endocytosis mechanism resulted in the lysosomal entrapment of these NPs within the cell. γ-PGA_SS_ADH_Cur NPs exhibited a dual stimuli responsive drug delivery and can be used as a smart and potential drug delivery system in cancer microenvironment.

Objective: The current study investigates the potential of alcoholic extract of Wrightia tinctoria leaves and its isolates in repairing the DNA damage induced by gamma radiation. Methodology: The ethanolic extract of Wrightia tinctoria (EEWT) the leaves was subjected to in vitro anti oxidant assay by DPPH radical scavenging and hydrogen peroxide scavenging methods. He EEWT was investigated to the Micronucleus assay, spleen colony assay and comet assay in Sprague Dawley rats wherein DNA damage had already been induced by irradiation. Results: The ethanolic extract of Wrightia tinctoria leaves having good antioxidant activity. In the micronucleus assay, a 2 Gy quantum of whole-body gamma radiation significantly enhanced the levels of micronucleated reticulocytes and this induction was substantially reversed in the extract treatment group. Results of the spleen colony assay pointed to the extract's ability to enhance the recovery of the hematopoietic system, in a dose-dependent manner, following 6 Gy gamma irradiation. The decrease in cellular repair index due to enhanced DNA repair was evident from the comet assay parameters. Moreover, the isolates from ethanolic extract of Wrightia tinctoria, when imperiled to DNA protection by in vitro gamma radiation method in plasmid pBR322 DNA, abetted DNA repair at higher dose. Conclusion: The DNA protection afforded is likely attributable to free radical scavenging properties along with a potential for regenerating the immune system through repair of post irradiated DNA. © 2016, EManuscript Services. All rights reserved.

Pancreatic cancer is a class of disease characterized by uncontrolled cell growth that begins in the pancreas. Heat shock proteins (Hsps) are chaperone proteins that on inhibition can prove to be effective in pancreatic cancer treatment. In cancer cells, Hsp90 significantly displays a proliferative potential of the malignant cells, so the inhibition of the protein can prove to be valuable to combat pancreatic cancer. Computer Aided Drug Designing (CADD) was instrumental to find out the effective constituent among the 35 plant sources selected. The Phytochemicals used for the present study were Curcumin, Allicin, Pinene, Tetrahydrocannabinol, Astragalin, Arginine, Scopoletin, Baicalin, Stylopine, Carvacrol, Quercetin, Thymol, Guaiaretic acid, Coumarin, Chlorogenic acid, Taraxacin, Ascorbic acid, Protocatechuic acid, Withaferin A, Triptolide, Ursolic acid, Cucurbitane, Thymoquinone, D-Carvone, Eugenol, Ellagic acid, Lapachol, Genistein, Emodin, Chelidonine, Caffeine, Catechin, Geraniol, Myrcene and Niacin. The preliminary studies such as the Primary and Secondary structure analysis of the protein were carried out. Molecular property based on Lipinski rule of 5, bioactivity parameters as well as Protein-Ligand Dynamic interaction were analyzed to determine the drug likeness of the ligands with the protein 4L94. The results of the in silico docking analysis indicate the selection of natural compounds such as Cucurbitane, Myrcene and Pinene as they elicited significant binding interaction in inhibiting Heat shock proteins for targeting pancreatic cancer which was comparable with that of the standard drug Gemcitabine. Further in vivo studies may be carried out to prove the same.