Synthesis of new 1,2-disubstituted benzimidazole analogs as potent inhibitors of Î-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...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
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Elsevier B.V.
2021
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| Online Access: | http://psasir.upm.edu.my/id/eprint/95271/ |
| _version_ | 1848862115514810368 |
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| author | Muhammad Taha Ahmad Khan, Aftab Rahim, Fazal Imran, Syahrul Mohammed Salahuddin Uddin, Nizam Mohammed Khan, Khalid Ali Shah, Syed Adnan Zafar, Ameeduzzafar Zakaria, Zainul Amiruddin |
| author_facet | Muhammad Taha Ahmad Khan, Aftab Rahim, Fazal Imran, Syahrul Mohammed Salahuddin Uddin, Nizam Mohammed Khan, Khalid Ali Shah, Syed Adnan Zafar, Ameeduzzafar Zakaria, Zainul Amiruddin |
| author_sort | Muhammad Taha |
| building | UPM Institutional Repository |
| collection | Online Access |
| 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. |
| first_indexed | 2025-11-15T13:11:54Z |
| format | Article |
| id | upm-95271 |
| institution | Universiti Putra Malaysia |
| institution_category | Local University |
| last_indexed | 2025-11-15T13:11:54Z |
| publishDate | 2021 |
| publisher | Elsevier B.V. |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | upm-952712023-04-12T01:41:03Z http://psasir.upm.edu.my/id/eprint/95271/ Synthesis of new 1,2-disubstituted benzimidazole analogs as potent inhibitors of Î-Glucuronidase and in silico study Muhammad Taha Ahmad Khan, Aftab Rahim, Fazal Imran, Syahrul Mohammed Salahuddin Uddin, Nizam Mohammed Khan, Khalid Ali Shah, Syed Adnan Zafar, Ameeduzzafar Zakaria, Zainul Amiruddin 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. Elsevier B.V. 2021 Article PeerReviewed Muhammad Taha and Ahmad Khan, Aftab and Rahim, Fazal and Imran, Syahrul and Mohammed Salahuddin and Uddin, Nizam and Mohammed Khan, Khalid and Ali Shah, Syed Adnan and Zafar, Ameeduzzafar and Zakaria, Zainul Amiruddin (2021) Synthesis of new 1,2-disubstituted benzimidazole analogs as potent inhibitors of Î-Glucuronidase and in silico study. Arabian Journal of Chemistry, 15 (1). pp. 1-15. ISSN 1878-5352 https://www.sciencedirect.com/science/article/pii/S1878535221005207?via%3Dihub 10.1016/j.arabjc.2021.103505 |
| spellingShingle | Muhammad Taha Ahmad Khan, Aftab Rahim, Fazal Imran, Syahrul Mohammed Salahuddin Uddin, Nizam Mohammed Khan, Khalid Ali Shah, Syed Adnan Zafar, Ameeduzzafar Zakaria, Zainul Amiruddin Synthesis of new 1,2-disubstituted benzimidazole analogs as potent inhibitors of Î-Glucuronidase and in silico study |
| title | Synthesis of new 1,2-disubstituted benzimidazole analogs as potent inhibitors of Î-Glucuronidase and in silico study |
| title_full | Synthesis of new 1,2-disubstituted benzimidazole analogs as potent inhibitors of Î-Glucuronidase and in silico study |
| title_fullStr | Synthesis of new 1,2-disubstituted benzimidazole analogs as potent inhibitors of Î-Glucuronidase and in silico study |
| title_full_unstemmed | Synthesis of new 1,2-disubstituted benzimidazole analogs as potent inhibitors of Î-Glucuronidase and in silico study |
| title_short | Synthesis of new 1,2-disubstituted benzimidazole analogs as potent inhibitors of Î-Glucuronidase and in silico study |
| title_sort | synthesis of new 1,2-disubstituted benzimidazole analogs as potent inhibitors of î-glucuronidase and in silico study |
| url | http://psasir.upm.edu.my/id/eprint/95271/ http://psasir.upm.edu.my/id/eprint/95271/ http://psasir.upm.edu.my/id/eprint/95271/ |