Synthesis of benzimidazole derivatives as potent β-glucuronidase inhibitors |
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| Institution: | 1. Atta-ur-Rahman Institute for Natural Product Discovery, Universiti Teknologi MARA (UiTM), Puncak Alam Campus, 42300 Bandar Puncak Alam, Selangor, Malaysia;2. Faculty of Applied Science, Universiti Teknologi MARA (UiTM), 40450 Shah Alam, Selangor, Malaysia;3. Integrative Pharmacogenomics Institute (iPROMISE), Universiti Teknologi MARA (UiTM), Puncak Alam Campus, 42300 Bandar Puncak Alam, Selangor Darul Ehsan, Malaysia;4. Faculty of Pharmacy, Universiti Teknologi MARA (UiTM), Puncak Alam Campus, 42300 Bandar Puncak Alam, Selangor Darul Ehsan, Malaysia;5. Department of Chemistry, Hazara University, Mansehra, Khyber Pakhtunkhwa, Pakistan;6. Pharmacology and Toxicology Research Laboratory, Faculty of Pharmacy, University Technology MARA (UiTM), 42300 Bandar Puncak Alam, Selangor Darul Ehsan, Malaysia;7. Department of Chemistry, COMSATS Institute of Information Technology, University Road, Abbottabad 22060, KPK, Pakistan;8. Center for Advanced Drug Research, COMSATS Institute of Information Technology, University Road, Abbottabad 22060, KPK, Pakistan;1. Department of Chemistry, Hazara University, Mansehra 21300, Pakistan;2. Department of Clinical Pharmacy, Institute for Research and Medical Consultations (IRMC), Imam Abdulrahman Bin Faisal University, P.O. Box 1982, Dammam 31441, Saudi Arabia;3. Department of Biochemistry, Abdul Wali Khan University Mardan, Mardan 23200, Pakistan;4. Atta-ur-Rahman Institute for Natural Product Discovery, Universiti Teknologi MARA (UiTM), Puncak Alam Campus, 42300 Bandar, Puncak Alam, Selangor D. E, Malaysia;5. Faculty of Pharmacy, Universiti Teknologi MARA (UiTM), Puncak Alam Campus, 42300 Bandar, Puncak Alam, Selangor Darul Ehsan, Malaysia;6. College of Computer Science & Information Technology (CCSIT), Imam Abdulrahman Bin Faisal University, P.O. Box 1982, Dammam 3144, Saudi Arabia;7. Department of Pharmacy, University of Malakand, Chakdara, Dir (L), Khyber-Pakhtunkhwa (KPK) 18000, Pakistan;8. Department of Pharmacy, Sarhad University of Science & Information Technology, Peshawar, Pakistan;1. H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan;2. Atta-ur-Rahman Institute for Natural Product Discovery, Universiti Teknologi MARA (UiTM), Puncak Alam Campus, 42300 Bandar Puncak Alam, Selangor D.E., Malaysia;3. Faculty of Applied Science, Universiti Teknologi MARA, Shah Alam 40450, Selangor D.E., Malaysia;4. PCSIR Laboratories Complex, Karachi, Shahrah-e-Dr. Salimuzzaman Siddiqui, Karachi 75280, Pakistan;5. Department of Biochemistry, Computational Medicinal Chemistry Laboratory, UCSS, Abdul Wali Khan University Mardan, Pakistan;1. Atta-ur-Rahman Institute for Natural Product Discovery, Universiti Teknologi MARA (UiTM), Puncak Alam Campus, 42300 Bandar Puncak Alam, Selangor, Malaysia;2. Faculty of Applied Science, Universiti Teknologi MARA (UiTM), 40450 Shah Alam, Selangor, Malaysia;3. Integrative Pharmacogenomics Institute (iPROMISE), Universiti Teknologi MARA (UiTM), Puncak Alam Campus, 42300 Bandar Puncak Alam, Selangor Darul Ehsan, Malaysia;4. Faculty of Pharmacy, Universiti Teknologi MARA (UiTM), Puncak Alam Campus, 42300 Bandar Puncak Alam, Selangor Darul Ehsan, Malaysia;5. Department of Chemistry, COMSATS Institute of Information Technology, University Road, Abbottabad 22060, KPK, Pakistan;6. H. E. J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan;7. Department of Chemistry, Hazara University, 21300 Mansehra, Pakistan;1. Department of Pharmaceutical Sciences, ASBASJSM College of Pharmacy, Bela, Ropar, Punjab, India;2. Drug Discovery Research, Panacea Biotec Pvt. Ltd., Mohali, Punjab, India;3. Rayat-Bahra Institute of Pharmacy, Hoshiarpur, Punjab, India;1. Dalian Medical University, Dalian 116044, China;2. Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China;3. Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China;4. Zhengzhou University of Light Industry, Zhengzhou 450001, China |
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| Abstract: | Twenty five 4, 6-dichlorobenzimidazole derivatives (1–25) have been synthesized and evaluated against β-glucuronidase inhibitory activity. The compounds which actively inhibit β-glucuronidase activity have IC50 values ranging between 4.48 and 46.12 μM and showing better than standard d-saccharic acid 1,4 lactone (IC50 = 48.4 ± 1.25 μM). Molecular docking provided potential clues to identify interactions between the active molecules and the enzyme which further led us to identify plausible binding mode of all the benzimidazole derivatives. This study confirmed that presence of hydrophilic moieties is crucial to inhibit the human β-glucuronidase. |
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| Keywords: | Benzimidazole Synthesis Docking studies |
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