2. Academic Validation
  3. FabI (enoyl acyl carrier protein reductase) - A potential broad spectrum therapeutic target and its inhibitors

FabI (enoyl acyl carrier protein reductase) - A potential broad spectrum therapeutic target and its inhibitors

  • Eur J Med Chem. 2020 Dec 15:208:112757. doi: 10.1016/j.ejmech.2020.112757.
Preeti Rana 1,  Shaik Mahammad Ghouse 1,  Ravikumar Akunuri 1,  Y V Madhavi 1,  Sidharth Chopra 2,  Srinivas Nanduri 3
Affiliations

Affiliations

  • 1 Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad, 500 037, India.
  • 2 Division of Microbiology, CSIR-Central Drug Research Institute, Sitapur Road, Sector 10, Janakipuram Extension, Lucknow, 226 031, Uttar Pradesh, India. Electronic address: skchopra.007@cdri.res.in.
  • 3 Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad, 500 037, India. Electronic address: nanduri.niperhyd@gov.in.
PMID: 32883635 DOI: 10.1016/j.ejmech.2020.112757
Abstract

Development of new anti-bacterial agents acting upon underexploited targets and thus evading known mechanisms of resistance is the need of the hour. The highly conserved and distinct Bacterial fatty acid biosynthesis pathway (FAS-II), presents a validated and yet relatively underexploited target for drug discovery. FabI and its isoforms (FabL, FabK, FabV and InhA) are essential enoyl-ACP reductases present in several Microorganisms. In addition, the components of the FAS-II pathway are distinct from the multi-enzyme FAS-I complex found in mammals. Thus, inhibition of FabI and its isoforms is anticipated to result in broad-spectrum Antibacterial activity. Several research groups from industry and academic laboratories have devoted significant efforts to develop effective FabI-targeting Antibiotics, which are currently in various stages of clinical development for the treatment of multi-drug resistant Bacterial infections. This review summarizes all the natural as well as synthetic inhibitors of gram-positive and gram-negative enoyl ACP reductases (FabI). The knowledge of the reported inhibitors can aid in the development of broad-spectrum antibacterials specifically targeting FabI Enzymes from S. aureus, S. epidermidis, B. anthracis, B. cereus, E. coli, P. aeruginosa, P. falciparum and M. tuberculosis.

Keywords

Antimicrobial resistance; Enoyl acyl carrier protein reductase; FAS-II; FabI; FabI inhibitors; Multidrug-resistant bacteria.

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