Synthesis and molecular docking study of piperazine derivatives as potent inhibitor of thymidine phosphorylase

Imad Uddin, Muhammad Taha, Fazal Rahim, Abdul Wadood

Index: 10.1016/j.bioorg.2018.03.026

Full Text: HTML

Abstract

Thymidine phosphorylase triggers the phosphorylation of pyrimidine base to thymine and 2-deoxyribose 1-phosphate which undergoes dephosphorylation to 2-deoxyribose. It plays a role in tumor angiogenesis which is referred to the development of blood vessels during tumor growth and therefore is an attractive drug target. Keeping in view the greater importance of its inhibition, here in this study we have synthesized piperazine analogs (1–18) and evaluated for thymidine phosphorylase inhibitory activity. All analogs showed potent inhibitory potential with IC50 values ranging between 0.2 ± 0.01 and 42.20 ± 0.70 µM when compared with standard 7-Deazaxanthine (IC50 value of 38.68 ± 1.12 µM). Structure activity relationship has been also established for all newly synthesized compounds. Molecular docking studies revealed that these compounds established stronger hydrogen bonding networks with active site residues of enzyme.