TY - JOUR
T1 - Synthesis of benzimidazole derivatives as potent β-glucuronidase inhibitors
AU - Taha, Muhammad
AU - Ismail, Nor Hadiani
AU - Imran, Syahrul
AU - Selvaraj, Manikandan
AU - Rashwan, Hesham
AU - Farhanah, Fatin Ummi
AU - Rahim, Fazal
AU - Kesavanarayanan, Krishnan Selvarajan
AU - Ali, Muhammad
N1 - Funding Information:
Authors would like to acknowledge The Ministry of Agriculture (MOA) Malaysia and Universiti Teknologi MARA for the financial support under MOA grant file No. 100-RMI/MOA 16/6/2 (1/2013) and Atta-ur-Rahman Institute for Natural product Discovery (RiND) to provide excellent designed lab and facility for the research and all technical and non-technical staff for a lot of support for this work.
Publisher Copyright:
© 2015 Elsevier Inc. All rights reserved.
Copyright:
Copyright 2015 Elsevier B.V., All rights reserved.
PY - 2015/6/12
Y1 - 2015/6/12
N2 - 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.
AB - 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.
KW - Benzimidazole
KW - Docking studies
KW - Synthesis
KW - β-Glucuronidase
UR - https://www.scopus.com/pages/publications/84930958744
U2 - 10.1016/j.bioorg.2015.05.010
DO - 10.1016/j.bioorg.2015.05.010
M3 - Article
C2 - 26073618
AN - SCOPUS:84930958744
SN - 0045-2068
VL - 61
SP - 36
EP - 44
JO - Bioorganic Chemistry
JF - Bioorganic Chemistry
ER -