Synthesis of Thymidine Phosphorylase Inhibitor Based on Quinoxaline Derivatives and Their Molecular Docking Study

摘要

We have synthesized quinoxaline analogs (>1–>25), characterized by ¹H-NMR and HREI-MS and evaluated for thymidine phosphorylase inhibition. Among the series, nineteen analogs showed better inhibition when compared with the standard inhibitor 7-Deazaxanthine (IC50 = 38.68 ± 4.42 µM). The most potent compound among the series is analog >25 with IC50 value 3.20 ± 0.10 µM. Sixteen analogs >1, >2, >3, >4, >5, >6, >7, >12, >13, >14, >15, >16, >17, >18, >21 and >24 showed outstanding inhibition which is many folds better than the standard 7-Deazaxanthine. Two analogs >8 and >9 showed moderate inhibition. A structure-activity relationship has been established mainly based upon the substitution pattern on the phenyl ring. The binding interactions of the active compounds were confirmed through molecular docking studies.