Ebrahim Saeedian Moghadam1, Abdullah Mohammed Al-Sadi2, Meysam Talebi3, Massoud Amanlou3,4, Mohsen Amini5,6, Raid Abdel-Jalil7. 1. Department of Chemistry, College of Science, Sultan Qaboos University, P.O. Box 36, P.C. 123, Muscat, Sultanate of Oman. 2. Department of Crop Sciences, College of Agricultural and Marine Sciences, Sultan Qaboos University, Muscat, Oman. 3. Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, 1417614411, Tehran, Iran. 4. Drug Design and Development Research Center, The Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences, 1417614411, Tehran, Iran. 5. Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, 1417614411, Tehran, Iran. moamini@tums.ac.ir. 6. Drug Design and Development Research Center, The Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences, 1417614411, Tehran, Iran. moamini@tums.ac.ir. 7. Department of Chemistry, College of Science, Sultan Qaboos University, P.O. Box 36, P.C. 123, Muscat, Sultanate of Oman. jalil@squ.edu.om.
Abstract
BACKGROUND: Benzimidazole derivatives are widely used to design and synthesize novel bioactive compounds. There are several approved benzimidazole-based drugs on the market. OBJECTIVES: In this study, we aimed to design and synthesize a series of novel benzimidazole derivatives 8a-n that are urease inhibitors. METHODS: All 8a-n were synthesized in a multistep. To determine the urease inhibitory effect of 8a-n, the urease inhibition kit was used. The cytotoxicity assay of 8a-n was determined using MTT method. Molecular modelling was determined using autodock software. RESULTS: All 8a-n were synthesized in high yield, and their structures were determined using 1H-NMR, 13C-NMR, MS, and elemental analyses. In compared to thiourea and hydroxyurea as standards (IC50: 22 and 100 µM, respectively), all 8a-n had stronger urease inhibition activity (IC50: 3.36-10.81 µM). With an IC50 value of 3.36 µM, 8e had the best enzyme inhibitory activity. On two evaluated cell lines, the MTT cytotoxicity experiment revealed that all 8a-n have IC50 values greater than 50 µM. Finally, a docking investigation revealed a plausible way of interaction between the 8e and 8d and the enzyme's active site's key residues. CONCLUSION: The synthesized benzimidazole derivatives exhibit high activity, suggesting that further research on this family of compounds would be beneficial to finding a potent urease inhibitor.
BACKGROUND: Benzimidazole derivatives are widely used to design and synthesize novel bioactive compounds. There are several approved benzimidazole-based drugs on the market. OBJECTIVES: In this study, we aimed to design and synthesize a series of novel benzimidazole derivatives 8a-n that are urease inhibitors. METHODS: All 8a-n were synthesized in a multistep. To determine the urease inhibitory effect of 8a-n, the urease inhibition kit was used. The cytotoxicity assay of 8a-n was determined using MTT method. Molecular modelling was determined using autodock software. RESULTS: All 8a-n were synthesized in high yield, and their structures were determined using 1H-NMR, 13C-NMR, MS, and elemental analyses. In compared to thiourea and hydroxyurea as standards (IC50: 22 and 100 µM, respectively), all 8a-n had stronger urease inhibition activity (IC50: 3.36-10.81 µM). With an IC50 value of 3.36 µM, 8e had the best enzyme inhibitory activity. On two evaluated cell lines, the MTT cytotoxicity experiment revealed that all 8a-n have IC50 values greater than 50 µM. Finally, a docking investigation revealed a plausible way of interaction between the 8e and 8d and the enzyme's active site's key residues. CONCLUSION: The synthesized benzimidazole derivatives exhibit high activity, suggesting that further research on this family of compounds would be beneficial to finding a potent urease inhibitor.
Authors: Farida Begum; Noor Barak Almandil; Muhammad Arif Lodhi; Khalid Mohammed Khan; Abdul Hameed; Shahnaz Perveen Journal: Bioorg Med Chem Date: 2019-02-02 Impact factor: 3.641
Authors: Hanan Gaber Abdulwahab; Marwa F Harras; Nagwan Galal El Menofy; Amany M Hegab; Basma M Essa; Adli AbdAllah Selim; Tamer M Sakr; Heba S A El-Zahabi Journal: Bioorg Med Chem Date: 2020-09-12 Impact factor: 3.641