Synthesis of indole based acetohydrazide analogs: Their in vitro and in silico thymidine phosphorylase studies

In this study, a series of indole based acetohydrazide derivatives (1–22) were synthesized and characterized by ¹³C NMR, ¹H NMR and HREI-MS. The resulted derivatives were tested for thymidine phosphorylase inhibitory potential. These derivatives inhibited thymidine phosphorylase at different concentration ranging from 1.10 ± 0.10 to 41.10 ± 1.10 µM when compared with the standard 7-Deazaxanthine (IC₅₀ value 38.68 ± 1.12 µM). The compound 8 having OH group at 2, 4 and 6 position was found the most potent among the series with IC₅₀ 1.10 ± 0.10 µM. The structure activity relationships (SAR) has been established for all compounds keeping in the view the role of substitution and the effect of functional group which significantly affect thymidine phosphorylase activity. The nature of binding interactions of the most potent compounds and active sites of the enzymes was confirmed through molecular docking study.