TY - JOUR
T1 - Novel benzimidazole derivatives; synthesis, bioactivity and molecular docking study as potent urease inhibitors
AU - Saeedian Moghadam, Ebrahim
AU - Al-Sadi, Abdullah Mohammed
AU - Talebi, Meysam
AU - Amanlou, Massoud
AU - Amini, Mohsen
AU - Abdel-Jalil, Raid
N1 - Funding Information:
This research was funded by His Majesty’s Trust Fund, grant number SR/SCI/CHEM/19/01, and by the Research Council of Tehran University of Medical Sciences.
Publisher Copyright:
© 2021, Springer Nature Switzerland AG.
PY - 2022/1/18
Y1 - 2022/1/18
N2 - 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.
AB - 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.
KW - Benzimidazole
KW - Drug design
KW - Nitrogen heterocycles
KW - Synthesis
KW - Urease inhibitors
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U2 - 10.1007/s40199-021-00427-3
DO - 10.1007/s40199-021-00427-3
M3 - Article
C2 - 35040104
SN - 1560-8115
JO - DARU, Journal of Pharmaceutical Sciences
JF - DARU, Journal of Pharmaceutical Sciences
ER -