Inhibitors of alanine racemase enzyme: a review

Abstract

Alanine racemase is a fold type III PLP-dependent amino acid racemase enzyme catalysing the conversion of l-alanine to d-alanine utilised by bacterial cell wall for peptidoglycan synthesis. As there are no known homologs in humans, it is considered as an excellent antibacterial drug target. The standard inhibitors of this enzyme include O-carbamyl-d-serine, d-cycloserine, chlorovinyl glycine, alaphosphin, etc. d-Cycloserine is indicated for pulmonary and extra pulmonary tuberculosis but therapeutic use of drug is limited due to its severe toxic effects. Toxic effects due to off-target affinities of cycloserine and other substrate analogs have prompted new research efforts to identify alanine racemase inhibitors that are not substrate analogs. In this review, an updated status of known inhibitors of alanine racemase enzyme has been provided which will serve as a rich source of structural information and will be helpful in generating selective and potent inhibitor of alanine racemase.

Етіологічна Терапія Бактеріальних Пневмоній Сьогодні Та В Майбутньому 3. Антибактеріальні Препарати, Що Розробляються

“…Установлено, что D-циклосерин обладает вы-раженной активностью против микобактерий, однако его клиническое применение ограни-ченно из-за выраженной токсичности. Аналоги D-циклосерина и его производные могут стать но-вым терапевтическим инструментом лечения ле-гочных форм туберкулеза [2].…”

Environmental roles of microbial amino acid racemases

“…Peptidoglycan synthesis (Saito et al, 2007;Azam and Jayaram, 2015) Pseudomonas aeruginosa Methanococcus maripaludis Schizosaccharomyces pombe Amino acid catabolism (Uo et al, 2001;Moore and Leigh, 2005;He et al, 2011)…”

C-Terminal 1-Aminoethyltetrazole-Containing Oligopeptides as Novel Alanine Racemase Inhibitors

“…This enzyme plays a key role in the biosynthesis of bacterial peptidoglycan through its activity in the racemisation of l-alanine to d-alanine in bacteria. In the past, several alanine racemase inhibitors have been reported [3,4], and some have been applied as antimicrobial agents. Examples of these include l,l-alafosfalin (1), the more active prodrug form of the direct AlaR inhibitor l-fosfalin (2).…”