Cargando…

In Vitro Antimycobacterial Activity and Physicochemical Characterization of Diaryl Ether Triclosan Analogues as Potential InhA Reductase Inhibitors

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 di...

Descripción completa

Detalles Bibliográficos
Autores principales: Ibrahim, Tarek S., Taher, Ehab S., Samir, Ebtihal, M. Malebari, Azizah, Khayyat, Ahdab N., Mohamed, Mamdouh F. A., Bokhtia, Riham M., AlAwadh, Mohammed A., Seliem, Israa A., Asfour, Hani Z., Alhakamy, Nabil A., Panda, Siva S., AL-Mahmoudy, Amany M. M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7397076/
https://www.ncbi.nlm.nih.gov/pubmed/32650556
http://dx.doi.org/10.3390/molecules25143125
_version_ 1783565702837305344
author Ibrahim, Tarek S.
Taher, Ehab S.
Samir, Ebtihal
M. Malebari, Azizah
Khayyat, Ahdab N.
Mohamed, Mamdouh F. A.
Bokhtia, Riham M.
AlAwadh, Mohammed A.
Seliem, Israa A.
Asfour, Hani Z.
Alhakamy, Nabil A.
Panda, Siva S.
AL-Mahmoudy, Amany M. M.
author_facet Ibrahim, Tarek S.
Taher, Ehab S.
Samir, Ebtihal
M. Malebari, Azizah
Khayyat, Ahdab N.
Mohamed, Mamdouh F. A.
Bokhtia, Riham M.
AlAwadh, Mohammed A.
Seliem, Israa A.
Asfour, Hani Z.
Alhakamy, Nabil A.
Panda, Siva S.
AL-Mahmoudy, Amany M. M.
author_sort Ibrahim, Tarek S.
collection PubMed
description 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 IC(50) 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.
format Online
Article
Text
id pubmed-7397076
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-73970762020-08-05 In Vitro Antimycobacterial Activity and Physicochemical Characterization of Diaryl Ether Triclosan Analogues as Potential InhA Reductase Inhibitors Ibrahim, Tarek S. Taher, Ehab S. Samir, Ebtihal M. Malebari, Azizah Khayyat, Ahdab N. Mohamed, Mamdouh F. A. Bokhtia, Riham M. AlAwadh, Mohammed A. Seliem, Israa A. Asfour, Hani Z. Alhakamy, Nabil A. Panda, Siva S. AL-Mahmoudy, Amany M. M. Molecules Article 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 IC(50) 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. MDPI 2020-07-08 /pmc/articles/PMC7397076/ /pubmed/32650556 http://dx.doi.org/10.3390/molecules25143125 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Ibrahim, Tarek S.
Taher, Ehab S.
Samir, Ebtihal
M. Malebari, Azizah
Khayyat, Ahdab N.
Mohamed, Mamdouh F. A.
Bokhtia, Riham M.
AlAwadh, Mohammed A.
Seliem, Israa A.
Asfour, Hani Z.
Alhakamy, Nabil A.
Panda, Siva S.
AL-Mahmoudy, Amany M. M.
In Vitro Antimycobacterial Activity and Physicochemical Characterization of Diaryl Ether Triclosan Analogues as Potential InhA Reductase Inhibitors
title In Vitro Antimycobacterial Activity and Physicochemical Characterization of Diaryl Ether Triclosan Analogues as Potential InhA Reductase Inhibitors
title_full In Vitro Antimycobacterial Activity and Physicochemical Characterization of Diaryl Ether Triclosan Analogues as Potential InhA Reductase Inhibitors
title_fullStr In Vitro Antimycobacterial Activity and Physicochemical Characterization of Diaryl Ether Triclosan Analogues as Potential InhA Reductase Inhibitors
title_full_unstemmed In Vitro Antimycobacterial Activity and Physicochemical Characterization of Diaryl Ether Triclosan Analogues as Potential InhA Reductase Inhibitors
title_short In Vitro Antimycobacterial Activity and Physicochemical Characterization of Diaryl Ether Triclosan Analogues as Potential InhA Reductase Inhibitors
title_sort in vitro antimycobacterial activity and physicochemical characterization of diaryl ether triclosan analogues as potential inha reductase inhibitors
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7397076/
https://www.ncbi.nlm.nih.gov/pubmed/32650556
http://dx.doi.org/10.3390/molecules25143125
work_keys_str_mv AT ibrahimtareks invitroantimycobacterialactivityandphysicochemicalcharacterizationofdiarylethertriclosananaloguesaspotentialinhareductaseinhibitors
AT taherehabs invitroantimycobacterialactivityandphysicochemicalcharacterizationofdiarylethertriclosananaloguesaspotentialinhareductaseinhibitors
AT samirebtihal invitroantimycobacterialactivityandphysicochemicalcharacterizationofdiarylethertriclosananaloguesaspotentialinhareductaseinhibitors
AT mmalebariazizah invitroantimycobacterialactivityandphysicochemicalcharacterizationofdiarylethertriclosananaloguesaspotentialinhareductaseinhibitors
AT khayyatahdabn invitroantimycobacterialactivityandphysicochemicalcharacterizationofdiarylethertriclosananaloguesaspotentialinhareductaseinhibitors
AT mohamedmamdouhfa invitroantimycobacterialactivityandphysicochemicalcharacterizationofdiarylethertriclosananaloguesaspotentialinhareductaseinhibitors
AT bokhtiarihamm invitroantimycobacterialactivityandphysicochemicalcharacterizationofdiarylethertriclosananaloguesaspotentialinhareductaseinhibitors
AT alawadhmohammeda invitroantimycobacterialactivityandphysicochemicalcharacterizationofdiarylethertriclosananaloguesaspotentialinhareductaseinhibitors
AT seliemisraaa invitroantimycobacterialactivityandphysicochemicalcharacterizationofdiarylethertriclosananaloguesaspotentialinhareductaseinhibitors
AT asfourhaniz invitroantimycobacterialactivityandphysicochemicalcharacterizationofdiarylethertriclosananaloguesaspotentialinhareductaseinhibitors
AT alhakamynabila invitroantimycobacterialactivityandphysicochemicalcharacterizationofdiarylethertriclosananaloguesaspotentialinhareductaseinhibitors
AT pandasivas invitroantimycobacterialactivityandphysicochemicalcharacterizationofdiarylethertriclosananaloguesaspotentialinhareductaseinhibitors
AT almahmoudyamanymm invitroantimycobacterialactivityandphysicochemicalcharacterizationofdiarylethertriclosananaloguesaspotentialinhareductaseinhibitors