In vitro antimycobacterial activity and physicochemical characterization of diaryl ether triclosan analogues as potential inhA reductase inhibitors

Tarek S. Ibrahim, Ehab S. Tahe, Ebtihal Samir, Azizah M. Malebar, Ahdab N. Khayya, Mamdouh F.A. Mohamed, Riham M. Bokhti, Mohammed A. AlAwad, Israa A. Seliem, Hani Z. Asfou, Nabil A. Alhakamy, Siva S. Panda, Amany M.M. AL-Mahmoudy

Research output: Contribution to journalArticlepeer-review

Abstract

Two sets of diphenyl ether derivatives incorporating five-membered 1,3,4-oxadiazoles, and their open-chain aryl hydrazone analogs were synthesized in good yields. Most of the synthesized compounds showed promising in vitro antimycobacterial activity against Mycobacterium tuberculosis H37Rv. Three diphenyl ether derivatives, namely hydrazide 3, oxadiazole 4 and naphthylarylidene 8g exhibited pronounced activity with minimum inhibitory concentrations (MICs) of 0.61, 0.86 and 0.99 μg/mL, respectively compared to triclosan (10 μg/mL) and isoniazid (INH) (0.2 μg/mL). Compounds 3, 4, and 8g showed the InhA reductase enzyme inhibition with higher IC50 values (3.28-4.23 μM) in comparison to triclosan (1.10 μM). Correlation between calculated physicochemical parameters and biological activity has been discussed which justifies a strong correlation with respect to the inhibition of InhA reductase enzyme. Molecular modeling and drug-likeness studies showed good agreement with the obtained biological evaluation. The structural and experimental information concerning these three InhA inhibitors will likely contribute to the lead optimization of new antibiotics for M. tuberculosis.

Original languageEnglish (US)
Article number3125
JournalMolecules
Volume25
Issue number14
DOIs
StatePublished - Jul 2020

Keywords

  • Antitubercular agents
  • Diphenyl ether
  • H37Rv
  • InhA inhibitors
  • Molecular docking

ASJC Scopus subject areas

  • Analytical Chemistry
  • Chemistry (miscellaneous)
  • Molecular Medicine
  • Pharmaceutical Science
  • Drug Discovery
  • Physical and Theoretical Chemistry
  • Organic Chemistry

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