Thymidylate Kinase Inhibitors as Antibacterial Agents: A Review

• Published in: Applied biochemistry and microbiology Vol. 59; no. 3; pp. 250 - 266
• Main Authors: Jayanthi, K., Azam, M. A.
• Format: Journal Article
• Language: English
• Published: Moscow Pleiades Publishing 01.06.2023; Springer Nature B.V
• Subjects: Antibacterial activity; Antibacterial agents; Bacteria; Biochemistry; Biomedical and Life Sciences; Chemical synthesis; DNA biosynthesis; Information processing; Inhibitors; Kinases; Life Sciences; Literature reviews; Medical Microbiology; Microbiology; Nucleosides; Reviews; Thymidine; IC; MIC values; thymidine 5'-monophosphate; thymidylate kinase
• ISSN: 0003-6838; 1608-3024
• DOI: 10.1134/S0003683823030092

Bacterial thymidylate kinase (TMK) is a member of nucleoside monophosphate kinases and recently becomes a protein of interest in the discovery of new antibacterial agents. Thymidylate kinase is a highly conserved enzyme in the pyrimidine salvage pathway that catalyses the synthesis of thymidine 5'-triphosphate, an essential precursor for the synthesis of DNA-building block, thymidylate. Several scaffolds like bicyclic nucleosides, thiourea-substituted β-thymidines, benzyl thymines, thymidine analogues, naphthofuranones, imidazopyridinones, sulfonylpiperidines, fused cyanopyridone, piperidinyl thymines etc. have been investigated for their inhibitory activity against TMK from different bacterial strains. Several TMK inhibitors exhibited potent antibacterial activity, specifically against Mycobacterium tuberculosis , Staphylococcus aureus , Streptococcus pneumoniae, Enterococcus faecium and Enterococcus faecalis . In the present review we discuss bacterial TMK inhibitors, and their associated antibacterial activities reported in literature. This review provides a useful source of structural information which may be utilized for the design of TMK inhibitors possessing potent antibacterial activity.