title: Inhibitors of the peptidoglycan biosynthesis enzymes MurA-F.
abstract: The widespread emergence of resistant bacterial strains is becoming a serious threat to public health. This thus signifies the need for the development of new antibacterial agents with novel mechanisms of action. Continuous efforts in the design of novel antibacterials remain one of the biggest challenges in drug development. In this respect, the Mur enzymes, MurA-F, that are involved in the formation of UDP-N-acetylmuramyl-pentapeptide can be genuinely considered as promising antibacterial targets. This review provides an in-depth insight into the recent developments in the field of inhibitors of the MurA-F enzymes. Special attention is also given to compounds that act as multiple inhibitors of two, three or more of the Mur enzymes. Moreover, the reasons for the lack of preclinically successful inhibitors and the challenges to overcome these hurdles in the next years are also debated.
authors.affiliation: Faculty of Pharmacy, University of Ljubljana, Aškerčeva 7, 1000 Ljubljana, Slovenia.
authors.forename: Martina
authors.initials: M
authors.lastname: Hrast
authors.affiliation: Faculty of Pharmacy, University of Ljubljana, Aškerčeva 7, 1000 Ljubljana, Slovenia.
authors.forename: Izidor
authors.initials: I
authors.lastname: Sosič
authors.affiliation: Faculty of Pharmacy, University of Ljubljana, Aškerčeva 7, 1000 Ljubljana, Slovenia.
authors.forename: Roman
authors.initials: R
authors.lastname: Sink
authors.affiliation: Faculty of Pharmacy, University of Ljubljana, Aškerčeva 7, 1000 Ljubljana, Slovenia. Electronic address: stanislav.gobec@ffa.uni-lj.si.
authors.forename: Stanislav
authors.initials: S
authors.lastname: Gobec
mesh_terms: D019883:Alkyl and Aryl Transferases / Q000037:antagonists & inhibitors*; D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D010457:Peptidoglycan / Q000096:biosynthesis* / Q000737:chemistry*
chemical_list: D004791:Enzyme Inhibitors; D010457:Peptidoglycan; D019883:Alkyl and Aryl Transferases; C022566:UDP-N-acetylglucosamine 1-carboxyvinyltransferase
keywords: Antibiotics; Drug discovery; Enzyme inhibitors; Multiple inhibitors; Mur enzymes; Peptidoglycan