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MurD inhibitors as antibacterial agents: a review

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Abstract

Peptidoglycan is an essential component of the bacterial cell wall and is required for the survival of bacteria. ATP-dependent MurC–F ligases are responsible for the early stages of peptidoglycan biosynthesis. Second in the series, MurD catalyzes the addition of d-glutamic acid to UDP-MurNAc-l-Ala which involves acyl-phosphate and tetrahedral intermediates. Due to its high specificity for d-glutamic acid substrate and its absence in mammalian cells, MurD is considered as an attractive target for the design of novel antibacterial agents. Several MurD inhibitors have been designed and tested for their activity. These include phosphinates, N-acetylmuramic acids, pulvinones, phosphinodipeptide, cyclic nonapeptides, macrocyclic compounds, benzene-1,3-dicarboxylic acid, naphthalene sulphonamides, 2-thioxothiazolidin-4-ones, benzylidene-2,4-thiazolidindiones, etc. In the present review, an updated status of MurD enzyme inhibitors is presented which will serve as a useful source of structural information and 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

MRSA:

Methicillin-resistant Staphylococcus aureus

MIC:

Minimum inhibitory concentration

MurD:

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

UDP:

Uridine-5′-diphosphate

UMA:

Uridine-5′-diphosphate-N-acetylmuramoyl-l-alanine

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Acknowledgements

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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Correspondence to Mohammed Afzal Azam.

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Azam, M.A., Jupudi, S. MurD inhibitors as antibacterial agents: a review. Chem. Pap. (2020) doi:10.1007/s11696-020-01057-w

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Keywords

  • MurD enzyme
  • Naphthalene sulphonamides
  • Benzene-1,3-dicarboxylic acid
  • IC50
  • MIC