Benzothiazole-based 1,3,4-thiadiazole hybrids derivatives as effective inhibitors of urease and thymidine phosphorylase: Synthesis, in vitro and in silico approaches

Abstract

In the present era, the whole world suffered from varied diseases which are caused by different body enzymes. Among the different thymidine phosphorylase and urease are also produce negative effect on the body. In this regard various organic researchers tried to attempt varied moieties for enzyme inhibition, in the present study we have synthesized benzothiazole based thiadiazole derivatives (1–15) were characterized through 1HNMR, 13CNMR and HREI-MS. Moreover, these compounds were evaluated for biological profiles against thymidine phosphorylase and urease enzymes. Most of the compounds were found with significant potentials but some of them 2(IC50 = 5.70 ± 0.20 µM, 1.80 ± 0.20 µM), 5(IC50 = 4.50 ± 0.50 µM, 1.40 ± 0.10 µM), 6 (IC50 = 4.60 ± 0.20 µM, 2.50 ± 0.60 µM) and 12 (IC50 = 6.30 ± 0.20 µM, 3.10 ± 0.30 µM) exhibits excellent profile against both enzymes while compared with their standard drugs 7-Deazaxanthine, 7DX (IC50 = 13.68 ± 1.20 µM) and Thiourea(IC50 = 3.30 ± 1.30 µM) respectively. Docking studies for the potent compounds were also explored the binding interactions of ligand with active sites of enzymes.