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MurE inhibitors as antibacterial agents: a review

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Abstract

Peptidoglycan, an essential component of the bacterial cell wall plays a critical role in protecting bacteria against osmotic lysis. The ATP-dependent MurC-F ligases are crucial for the early stages of peptidoglycan biosynthesis. MurE ligase is third in the series and catalyzes the addition of l-Lysine (l-Lys) in Gram-positive bacteria or meso-diaminopimelic acid (meso-A2pm) in most Gram-negative bacteria to form UDP-N-acetylmuramoyl-l-Ala-d-Glu-l-Lys/A2pm. The high substrate specific for l-Lys or meso-A2pm makes this enzyme an attractive target for the development of antibacterial agents. Several MurE inhibitors have been reported including phosphinates, peptidosulfonamides, napthylfuran-2-ones, benzene-1,3-dicarboxylic acids, phosphorylatedhydroxyethylamines, natural compounds, 5-benzylidenethiazolidin-4-ones, N-alkyl-2-alkynyl-4(1H)-quinolones, rhodanine substituted d-glutamic acids, 2,5-dimethyl pyrroles, 2,5-disubstitued furans, tetrahydroisoquinolines etc. In the present review we present an update status and structural information of MurE enzyme inhibitors which may be utilized for the design of potent inhibitors against this enzyme.

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Abbreviations

ATP:

Adenosine triphosphate

d-Glu:

d-Glutamic acid

IC50 :

Half maximal inhibitory concentration

l-Ala:

l-Alanine

meso-A2pm:

meso-Diaminopimelic acid

MIC:

Minimum inhibitory concentration

MurE:

UDP-N-acetylmuramoyl-l-Ala:d-Glu ligase

UDP:

Uridine-5′-diphosphate

UDP-MurNAc:

UDP-N-acetylmuramic acid

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We would like to thank the Science and Engineering Research Board (SERB), Government of India for the financial support (No. EMR/2016/002981).

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  1. Department of Pharmaceutical Chemistry, JSS College of Pharmacy, JSS Academy of Higher Education and Research, Ooty, Nilgiris, Tamil Nadu, India

    Niladri Saha & Mohammed Afzal Azam

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  1. Niladri Saha
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Saha, N., Azam, M.A. MurE inhibitors as antibacterial agents: a review. J Incl Phenom Macrocycl Chem 98, 127–136 (2020). https://doi.org/10.1007/s10847-020-01018-6

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