title: Mur Ligase Inhibitors as Anti-bacterials: A Comprehensive Review.
abstract: Exploring a new target for antibacterial drug discovery has gained much attention because of the emergence of Multidrug Resistance (MDR) strains of bacteria. To overcome this problem the development of novel antibacterial was considered as highest priority task and was one of the biggest challenge since multiple factors were involved. The bacterial peptidoglycan biosynthetic pathway has been well documented in the last few years and has been found to be imperative source for the development of novel antibacterial agents with high target specificity as they are essential for bacterial survival and have no homologs in humans. We have therefore reviewed the process of peptidoglycan biosynthesis which involves various steps like formation of UDP-Nacetylglucosamine (GlcNAc), UDP-N-acetylmuramic acid (MurNAc) and lipid intermediates (Lipid I and Lipid II) which are controlled by various enzymes like GlmS, GlmM, GlmU enzyme, followed by Mur Ligases (MurAMurF) and finally by MraY and MurG respectively. These four amide ligases MurC-MurF can be used as the source for the development of novel multi-target antibacterial agents as they shared and conserved amino acid regions, catalytic mechanisms and structural features. This review begins with the need for novel antibacterial agents and challenges in their development even after the development of bacterial genomic studies. An overview of the peptidoglycan monomer formation, as a source of disparity in this process is presented, followed by detailed discussion of structural and functional aspects of all Mur enzymes and different chemical classes of their inhibitors along with their SAR studies and inhibitory potential. This review finally emphasizes on different patents and novel Mur inhibitors in the development phase.
authors.affiliation: Y. B. Chavan College of Pharmacy, Dr Rafiq Zakaria Campus, Rauza Baugh, Aurangabad-431001. India.
authors.forename: Jaiprakash N
authors.initials: JN
authors.lastname: Sangshetti
authors.affiliation: Yash Institute of Pharmacy, South City, Waluj Road, Aurangabad-431133. India.
authors.forename: Suyog S
authors.initials: SS
authors.lastname: Joshi
authors.affiliation: Department of Biotechnology, SavitribaiPhule University Pune, Pune-411007. India.
authors.forename: Rajendra H
authors.initials: RH
authors.lastname: Patil
authors.affiliation: Chemistry Research Laboratory, 12 Mansfield Road, Oxford, OX1 3TA. United Kingdom.
authors.forename: Mark G
authors.initials: MG
authors.lastname: Moloney
authors.affiliation: Shivaji University, Vidyanagar, Kolhapur-416004. India.
authors.forename: Devanand B
authors.initials: DB
authors.lastname: Shinde
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D055808:Drug Discovery; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D008025:Ligases / Q000037:antagonists & inhibitors*; D010457:Peptidoglycan / Q000096:biosynthesis
chemical_list: D000900:Anti-Bacterial Agents; D004791:Enzyme Inhibitors; D010457:Peptidoglycan; D008025:Ligases
keywords: Antibacterial agents; Chemical classes; Mur inhibitors; Peptidoglycan biosynthesis; SAR; patents.