Prediction of Thymidylate Synthase Inhibitors: An In Silico Study

Abstract

Human Thymidylate synthase (hTS) is among the most exploited enzymes in the modern structure based drug design of new anticancer agents due to its key role in the biosynthesis of DNA. Therefore, inhibition of hTS is considered to be a potent approach to cure many types of cancers. The most well-known hTS inhibitor is 5-fluorouracil which has been marketed as an anticancer drug, but more optimization is needed for its biological activity. In this work, six potential hTS inhibitors have been designed based on structure of 5-FU as a lead compound. The designed compounds were in silico investigated for their potency to inhibit hTS by using autodock vina. The results were showed that the designed compounds have binding modes similar to that of 5-FU, and most of them have robust binding affinities to hTs. Further molecular docking study was performed against dihydropyrimidine dehydrogenase to investigate whether the designed compounds are susceptible for degradation by this enzyme. The molecular docking study indicated that compounds 1-5 are the most potent ones.