Synthesis of new 1,2-disubstituted benzimidazole analogs as potent inhibitors of β-Glucuronidase and in silico study

New benzimidazole analogues (1–18) were synthesized and characterized through different spectroscopic techniques such as 1H NMR, 13C NMR and HREI-MS. All analogues were screened for β-glucuronidase inhibitory potential. All analogues showed varied degree of inhibitory potentials with IC50 values ran...

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Autores principales:	Muhammad Taha, Aftab Ahmad Khan, Fazal Rahim, Syahrul Imran, Mohammed Salahuddin, Nizam Uddin, Khalid Mohammed Khan, Syed Adnan Ali Shah, Ameeduzzafar Zafar, Zainul Amiruddin Zakaria
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2022
Materias:	Novel benzimidazole β-Glucuronidase enzyme inhibition Molecular docking Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/e982162410ef49c6bb3edb31ee059b99
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spelling	oai:doaj.org-article:e982162410ef49c6bb3edb31ee059b992021-11-06T04:24:29ZSynthesis of new 1,2-disubstituted benzimidazole analogs as potent inhibitors of β-Glucuronidase and in silico study1878-535210.1016/j.arabjc.2021.103505https://doaj.org/article/e982162410ef49c6bb3edb31ee059b992022-01-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S1878535221005207https://doaj.org/toc/1878-5352New benzimidazole analogues (1–18) were synthesized and characterized through different spectroscopic techniques such as 1H NMR, 13C NMR and HREI-MS. All analogues were screened for β-glucuronidase inhibitory potential. All analogues showed varied degree of inhibitory potentials with IC50 values ranging between 1.10 ± 0.10 to 39.60 ± 0.70 μM when compared with standard D-saccharic acid-1,4- lactone having IC50 value 48.30 μM. Analogues 17, 11, 9, 6, 1 and 13 having IC50 values 1.10 ± 0.10, 1.70 ± 0.10, 2.30 ± 0.10, 5.30 ± 0.20, 6.20 ± 0.20 and 8.10 ± 0.20 μM respectively, showed excellent β-glucuronidase inhibitory potential many folds better than the standard. All other analogues also showed good inhibitory potential better as compared to standard. Structure activity relationships (SAR) has been established for all compounds. The results from molecular docking studies supports the established SAR and developed a strong correlation with the results from in to vitro assay. The molecular docking results clearly highlighted how substituents like nitro and chloro affect the binding position of the active compounds in the active site. The docking results were also used to properly establish the effect of bulky substituents of least active compounds on reduced β-glucuronidase inhibitory activity. Compounds 1–18 were found non-toxic.Muhammad TahaAftab Ahmad KhanFazal RahimSyahrul ImranMohammed SalahuddinNizam UddinKhalid Mohammed KhanSyed Adnan Ali ShahAmeeduzzafar ZafarZainul Amiruddin ZakariaElsevierarticleNovel benzimidazoleβ-Glucuronidase enzyme inhibitionMolecular dockingChemistryQD1-999ENArabian Journal of Chemistry, Vol 15, Iss 1, Pp 103505- (2022)
institution	DOAJ
collection	DOAJ
language	EN
topic	Novel benzimidazole β-Glucuronidase enzyme inhibition Molecular docking Chemistry QD1-999
spellingShingle	Novel benzimidazole β-Glucuronidase enzyme inhibition Molecular docking Chemistry QD1-999 Muhammad Taha Aftab Ahmad Khan Fazal Rahim Syahrul Imran Mohammed Salahuddin Nizam Uddin Khalid Mohammed Khan Syed Adnan Ali Shah Ameeduzzafar Zafar Zainul Amiruddin Zakaria Synthesis of new 1,2-disubstituted benzimidazole analogs as potent inhibitors of β-Glucuronidase and in silico study
description	New benzimidazole analogues (1–18) were synthesized and characterized through different spectroscopic techniques such as 1H NMR, 13C NMR and HREI-MS. All analogues were screened for β-glucuronidase inhibitory potential. All analogues showed varied degree of inhibitory potentials with IC50 values ranging between 1.10 ± 0.10 to 39.60 ± 0.70 μM when compared with standard D-saccharic acid-1,4- lactone having IC50 value 48.30 μM. Analogues 17, 11, 9, 6, 1 and 13 having IC50 values 1.10 ± 0.10, 1.70 ± 0.10, 2.30 ± 0.10, 5.30 ± 0.20, 6.20 ± 0.20 and 8.10 ± 0.20 μM respectively, showed excellent β-glucuronidase inhibitory potential many folds better than the standard. All other analogues also showed good inhibitory potential better as compared to standard. Structure activity relationships (SAR) has been established for all compounds. The results from molecular docking studies supports the established SAR and developed a strong correlation with the results from in to vitro assay. The molecular docking results clearly highlighted how substituents like nitro and chloro affect the binding position of the active compounds in the active site. The docking results were also used to properly establish the effect of bulky substituents of least active compounds on reduced β-glucuronidase inhibitory activity. Compounds 1–18 were found non-toxic.
format	article
author	Muhammad Taha Aftab Ahmad Khan Fazal Rahim Syahrul Imran Mohammed Salahuddin Nizam Uddin Khalid Mohammed Khan Syed Adnan Ali Shah Ameeduzzafar Zafar Zainul Amiruddin Zakaria
author_facet	Muhammad Taha Aftab Ahmad Khan Fazal Rahim Syahrul Imran Mohammed Salahuddin Nizam Uddin Khalid Mohammed Khan Syed Adnan Ali Shah Ameeduzzafar Zafar Zainul Amiruddin Zakaria
author_sort	Muhammad Taha
title	Synthesis of new 1,2-disubstituted benzimidazole analogs as potent inhibitors of β-Glucuronidase and in silico study
title_short	Synthesis of new 1,2-disubstituted benzimidazole analogs as potent inhibitors of β-Glucuronidase and in silico study
title_full	Synthesis of new 1,2-disubstituted benzimidazole analogs as potent inhibitors of β-Glucuronidase and in silico study
title_fullStr	Synthesis of new 1,2-disubstituted benzimidazole analogs as potent inhibitors of β-Glucuronidase and in silico study
title_full_unstemmed	Synthesis of new 1,2-disubstituted benzimidazole analogs as potent inhibitors of β-Glucuronidase and in silico study
title_sort	synthesis of new 1,2-disubstituted benzimidazole analogs as potent inhibitors of β-glucuronidase and in silico study
publisher	Elsevier
publishDate	2022
url	https://doaj.org/article/e982162410ef49c6bb3edb31ee059b99
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Synthesis of new 1,2-disubstituted benzimidazole analogs as potent inhibitors of β-Glucuronidase and in silico study

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