SYNTHESIS OF QUINOLINYL-OXADIAZOLE AS A POTENT ANTIBACTERIAL AGENT AND SA-FABI INHIBITOR

  • Dhanya Sunil Department of Chemistry, Manipal Institute of Technology, Manipal University, Manipal 576104, India
  • Laveeta D’almeida Department of Chemistry, Manipal Institute of Technology, Manipal University, Manipal 576104, India
  • Suvarna G Kini Department of Pharmaceutical Chemistry, Manipal College of Pharmaceutical Sciences, Manipal University, India
  • Rama M Department of Pharmaceutical Chemistry, Manipal College of Pharmaceutical Sciences, Manipal University, India

Abstract

Objective: Microbial resistance to currently marketed drugs is a serious problem worldwide and there is a vital need to develop novel antibiotics. Enoyl-ACP reductase (FabI) is essential for fatty acid biosynthesis and hence serves as an appealing target for antibacterials against methicillin resistant S. aureus. The present study focuses on the synthesis, antibacterial and saFab1 docking studies of three new series of quinoline derivatives: 5-[(quinolin-8-yloxy) methyl]-1,3,4-oxadiazole-2(3H)-thiones, N-(2,5-dimethyl-1H-pyrrol-1-yl)-2oxyacetamides and 2-(oxyacetyl)-5-methyl-2,4-dihydro-3H-pyrazol-3-ones with integrated ether linkages.

Methods: Three different substituted hydrazides were synthesized from substituted quinolinols. These hydrazides were allowed to undergo further reactions with carbon disulphide, 2,5-hexanedione and ethyl acetoacetate respectively to prepare 1,3,4-oxadiazole-2-thiones, N-substituted pyrrole acetamides and pyrazol-3-ones. The synthesized hydrazide derivatives were subjected to antimicrobial studies against Staphylococcus aureus. Docking studies were carried out using enoyl-ACP reductase crystal structure complexed with NADPH.

Results: 5-{[(2-methylquinolin-8-yl) oxy] methyl}-1, 3, 4-oxadiazole-2(3H)-thione (2b) with a methyl substituent on the quinoline ring was found to display significant antibacterial potential against S. aureus. Good binding interactions were observed in subsequent docking studies via formation of Fab1-NAD+-2b ternary complex through hydrogen bonding and stacking interactions.

Conclusion: 1, 3, 4-oxadiazole-2(3H)-thione (2b) was found to exhibit promising antibacterial potential against S. aureus.

 

Keywords: Oxadiazole, Antibacterial, saFab1, Triclosan

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Sunil, D., D’almeidaL., S. G. Kini, and R. M. “SYNTHESIS OF QUINOLINYL-OXADIAZOLE AS A POTENT ANTIBACTERIAL AGENT AND SA-FABI INHIBITOR”. International Journal of Pharmacy and Pharmaceutical Sciences, Vol. 8, no. 8, June 2015, pp. 105-9, https://innovareacademics.in/journals/index.php/ijpps/article/view/6634.
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