Thymidine phosphorylase and prostrate cancer cell proliferation inhibitory activities of synthetic 4-hydroxybenzohydrazides: In vitro, kinetic, and in silico studies.

ABSTRACT: Over-expression of thymidine phosphorylase (TP) plays a key role in many pathological complications, including angiogenesis which leads to cancer cells proliferation. Thus in search of new anticancer agents, a series of 4-hydroxybenzohydrazides (1-29) was synthesized, and evaluated for in vitro thymidine phosphorylase inhibitory activity. Twenty compounds 1-3, 6-14, 16, 19, 22-24, and 27-29 showed potent to weak TP inhibitory activities with IC50 values in the range of 6.8 to 229.5 μM, in comparison to the standards i.e. tipiracil (IC50 = 0.014 ± 0.002 μM) and 7-deazaxanthine (IC50 = 41.0 ± 1.63 μM). Kinetic studies on selected inhibitors 3, 9, 14, 22, 27, and 29 revealed uncompetitive and non-competitive modes of inhibition. Molecular docking studies of these inhibitors indicated that the

SUBMITTER: Javaid S 

PROVIDER: S-EPMC6984732 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature