Synthesis, in vitro thymidine phosphorylase activity and molecular docking study of thiadiazole bearing isatin analogs

A series of seventeen analogs (1─17) were synthesized and characterized through different spectroscopic techniques such as 1H, 13CNMR, HR-EI-MS and were evaluated for in vitro thymidine phosphorylase inhibition. All compounds showed excellent to good thymidine phosphorylase activity having IC50 value ranging between 4.10 ± 0.20 and 54.60 ± 1.40 µM when compared with standard drug 7-deazaxanthine (IC50 = 38.68 ± 1.12 µM). Among the series, compounds 1 (IC50 = 8.30 ± 0.30 µM), 6 (IC50 = 6.30 ± 0.10 µM), 11 (IC50 = 8.40 ± 0.30 µM) and 16 (IC50 = 4.10 ± 0.20 µM) were found more potent. Potent compounds were further subjected to molecular docking study to identify their interactions with the active site of amino acid. Structure activity relationship was done for all analogs mostly based on substitution pattern on phenyl and isatin rings.