Study of molecular docking of new fluorine derivatives as inhibitors thymidylate synthase enzyme

Cancer is a functional disorder that gradually causes the patient's abilities to decline. ۵-FU is used to treat a variety of cancers. The aim of this drug is to inhibit the enzyme thymidylate synthase(TS). TS enzyme is an enzyme essential for the synthesis of RNA, DNA, and apoptotic processes. The aim of this study is to investigate the inhibitory effect of fluorine derivatives on the activity of the enzyme thymidylate synthase is environmental in silico. To investigate how compounds bind to the active site of the enzyme, first the chemical structures of the compositions were designed using ChemDraw professional ۱۷.۱ software, then in order to optimize energy, Material Studio ۲۰۱۷ software was used. Docking studies were performed by Auto Dock Vina software and the results were analyzed using Discovery Studio software. The risk of toxicity of the compounds was assessed by OSIRIS software. Based on the results of docking studies, the most important bonds involved in drug- receptor binding are hydrogen bonds and van der Waals bonds. Among all the compounds studied, the best docking results are related to compound number ۸. Due to this compound, having a binding energy of -۶.۴, it had no risk of toxicity and had a high drug score, and a greater tendency to bind to key amino acids, the active site of the enzyme thymidylate synthase.

Keywords:

Thymidylate synthase , ۵-Fluorouracil , Molecular docking , Toxicity assessment , Fluorine derivatives