Molecules, Vol. 25, Pages 3125: In Vitro Antimycobacterial Activity and Physicochemical Characterization of Diaryl Ether Triclosan Analogues as Potential InhA Reductase Inhibitors

Molecules, Vol. 25, Pages 3125: In Vitro Antimycobacterial Activity and Physicochemical Characterization of Diaryl Ether Triclosan Analogues as Potential InhA Reductase Inhibitors Molecules doi: 10.3390/molecules25143125 Authors: Tarek Ibrahim Ehab Taher Ebtihal Samir Azizah Malebari Ahdab Khayyat Mamdouh Mohamed Riham Bokhtia Mohammed AlAwadh Israa Seliem Hani Asfour Nabil Alhakamy Siva Panda Amany AL-Mahmoudy 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 experimenta...
Source: Molecules - Category: Chemistry Authors: Tags: Article Source Type: research