Steric Complementarity of Conjugates of Some Derivatives of 5-Aminoand 5-Hydroxy-6-Methyluracil With Benzoic Acid With Thymidylate Kinase of the Human Herpes Simplex Virus Type 1

Abstract

The enzyme thymidylate kinase (TMPC, EC 2.7.4.9; dTMP kinase) belongs to the family of nucleoside monophosphate (NMP) kinases and in the presence of Mg 2+ ions catalyzes the formation of thymidine-5-diphosphate from thymidine 5'-monophosphate. This enzyme is well known as a potential drug target in the development of antiviral, antimicrobial, and antitumor drugs. In this work, the steric complementarity of 20 conjugates of derivatives of 5-aminouracil and 5-hydroxymethyluracil with benzoic acid with a general formula with the active center of thymidylate kinase of the human herpes simplex virus type 1 of TMPC was studied by molecular docking using the AutoDock Vina program.Practically all tested compounds are characterized by moderate numerical values of the free binding energy with the active center of TMPC E bind , comparable with a similar value for the natural substrate TMPC -TMR. These data suggest that the structures of the K1-K20 ligands are capable of replacing TMR in the active center of TMPC. Stabilization of compounds K1-K20 in the active site TMPK promotes the participation of these ligands in the formation of hydrogen bonds, alkyl and electrostatic interactions with the nearby ARG150, LEU53, VAL68, π-π stacking interactions with PHE72 and PHE105, π-alkyl interactions with PHE72, PRO43, and PHE156. Thus, all studied compounds are promising for further studies in vivo.