COMPUTATIONAL SCREENING AND SYNTHESIS OF SOME ISATIN-THIADIAZOLE HYBRIDS POTENTIALLY TARGATING DIABETES

Introduction: It is generally known that Thiadiazole derivatives, particularly those that inhibit Aldose reductase, Alpha amylase, Monoglycerol lipase and Glucagon like Peptide- 1, are strong antidiabetic agents. Glybuzole, Pioglitazone and other similar products are among the marketed goods.

Objective: In order to investigate the possibility of these compounds serving as multi-targeted enzyme receptor inhibitors. The molecules showcased in the current study were designed and synthesized as thiadiazole derivatives and further evaluated for in-silico Antidiabetic Activity.

Methods: The titled compounds as hybrid derivatives were prepared in two steps. First step involved synthesis of substituted thiadiazole intermediates using thiosemicarbazide. In second step, the final compounds were synthesisd using various substituted thiadiazoles and isatin in presence of ethanol and glacial acetic acid.

Results: The docking study was conducted for six synthesized compounds (2a-2f) and PDB Ids were procured and used as anti-diabetic targets 1US0 (aldose reductase), 4W93 (alpha amylase), 5UZN (monoglycerol lipase),and 3IOL (glycogen like protein), considering binding affinity, Lipinski's rule, and ADME properties through computational methods. All compounds passed the initial in silico screening. Among them, compounds 2a and 2b met Lipinski's criteria. Compound 2a showed the strongest binding affinity -10.6, -9.8, and -7.4, while 2b followed with -10.2, -9.4, -7.5 and -7.0. These results suggest that compounds 2a and 2b are promising candidates for further pre-clinical and in-vitro studies.

References:

1. Dhruzhinina, T.V.; Kondrashova, N.N.; Shvekhgeimer, M.G.A.; Synthesis of new derivatives of polycapromide graft copolymers containing 2‐(4‐Aminophenyl)Quinoline‐4‐carboxylic acid fragments. Fibre Chemistry. 36, 2004, 8‐11.