Background and purpose: Oxidative stress caused by cytokine exposure is a major cause of pancreatic islet death in vitro and of diabetogenesis. Antioxidant compounds may prevent cytokine-induced damage to islet cells. Hence, we studied the potential of curcumin, an antioxidant and anti-inflammatory compound, in vitro to protect islets against pro-inflammatory cytokines and in vivo to prevent the progression of diabetes induced by multiple low doses of streptozotocin (MLD-STZ). Experimental approach: Pancreatic islets from C57/BL6J mice were pretreated with curcumin (10 mM) and then exposed to a combination of cytokines. Islet viability, reactive oxygen species (ROS), NO, inducible NO synthase and NF-kB translocation were studied. Curcumin pretreated (7.5 mg kg À1 day À1 ) C57/BL6J mice were given MLD-STZ (40 mg kg À1 ), and various parameters of diabetes induction and progression were monitored. Key results: Curcumin protected islets from cytokine-induced islet death in vitro by scavenging ROS and normalized cytokineinduced NF-kB translocation by inhibiting phosphorylation of inhibitor of kappa B alpha (IkBa). In vivo, curcumin also prevented MLD-STZ, as revealed by sustained normoglycaemia, normal glucose clearance and maintained pancreatic GLUT2 levels. Pro-inflammatory cytokine concentrations in the serum and pancreas were raised in STZ-treated animals, but not in animals pretreated with curcumin before STZ. Conclusions and implications:Here, we have demonstrated for the first time that curcumin in vitro protects pancreatic islets against cytokine-induced death and dysfunction and in vivo prevents STZ-induced diabetes.

On account of the ever increasing resistance of M.tuberculosis strains to orthodox therapy regimens, the task of combating tuberculosis becomes even more challenging. Therefore, there arises a need to isolate new drug targets and subsequently design specific inhibitors for the same. In bacteria, algae, plants and fungi, the synthesis of Branched Chain Amino Acids (BCAAs) is catalyzed by Acetohydroxyacid Synthases (AHAS) group of enzymes. Bacterial AHAS (EC 2.2.1.6) catalyzes the biosynthesis of isoleucine, leucine and valine by utilizing cofactors like Thiamin Diphosphate (ThDP), Flavin Adenine Dinucleotide (FAD) and a divalent metal cation (Usually Mg(2+)). The anabolic form of the enzyme which is presently under discussion consists of two subunits out of which one is catalytic while the other is regulatory in nature. The product of this enzyme catalyzed reaction is either 2-acetolactate or 2-aceto-2-hydroxybutyrate obtained from self-condensation of pyruvate or condensation of puruvate and 2-ketobutyrate, respectively. These are further converted to the BCAAs by a series of other enzymes. The step catalyzed by AHAS is the first in the entire cascade and hence can be selectively targeted for the inhibition of this pathway. M.tuberculosis AHAS, which is encoded by the ilvB and ilvN operons is structurally related to E.coli AHAS and has a similar function. Therefore, specific drugs belonging to the classes of sulfonylureas, imidazolinones and benzoyl esters can be used as inhibitors of M.tuberculosis AHAS which would consequently deplete the BCAA supply to the bacteria. Thus, efficient bacteriostasis can be achieved.

Emergence of MDR-TB and XDR-TB led to the failure of available anti-tubercular drugs. In order to explore, identify and develop new anti-tubercular drugs, novel peptidomimetic series of Mtb-peptide deformylase (PDF) inhibitors was designed and synthesized. In vitro antimycobacterial potential of compounds was established by screening of compounds against Mycobacterium tuberculosis H37Rv strain using MABA. Among them, ester series of compounds 4a, 4b, 4c, 4d, and 4e were found most active, with compound 4c being highly active and exhibiting minimum inhibitory concentration of 6.25 µg/ml against M. tb H37Rv strain. Additionally, the compounds were docked to determine the probable binding interactions and understand the mechanism of action of most active molecules on Mtb-peptide deformylase (PDF), which is involved in the mycobacterium protein synthesis.

No abstract

We have developed novel series of 5-arylidene-1, 3-thiazolidin-4-one analogues using diethylamine as catalyst. Diethylamine was found suitable in synthesizing variety of title compounds in 62-85% yield. In-vitro anticancer activity of synthesized analogues was evaluated using human breast (MCF7), lung (Hop62) and hepatic (HepG2) cell lines using SRB assay. Amongst the synthesized compounds 9b, 9e, 9f are excellent in inhibiting growth of cancer cell lines with GI50 value <10μg/ml in comparison with Adriamycin standard. We have also performed docking studies using SHP2 in complex with inhibitor (PDB ID: 2Shp) but results were non-supportive, very weak. We found no correlation between anticancer studies and docking studies.