Synthesis, in vitro urease inhibitory potential and molecular docking study of Benzimidazole analogues

Khalid Zaman; Fazal Rahim; Muhammad Taha; Hayat Ullah; Abdul Wadood; Mohsan Nawaz; Fahad Khan; Zainul Wahab; Syed Adnan Ali Shah; Ashfaq Ur Rehman; Abdel-Nasser Kawde; Mohammed Gollapalli

doi:10.1016/j.bioorg.2019.103024

Synthesis, in vitro urease inhibitory potential and molecular docking study of Benzimidazole analogues

Bioorg Chem. 2019 Aug:89:103024. doi: 10.1016/j.bioorg.2019.103024. Epub 2019 May 31.

Authors

Affiliations

¹ Department of Chemistry, Hazara University, Mansehra 21300, Khyber Pakhtunkhwa, Pakistan.
² Department of Chemistry, Hazara University, Mansehra 21300, Khyber Pakhtunkhwa, Pakistan. Electronic address: fazalstar@gmail.com.
³ Department of Clinical Pharmacy, Institute for Research and Medical Consultations (IRMC), Imam Abdulrahman Bin Faisal University, P.O. Box 1982, Dammam 31441, Saudi Arabia. Electronic address: Mtaha@iau.edu.sa.
⁴ Department of Biochemistry, Abdul Wali Khan University Mardan, Mardan 23200, Pakistan.
⁵ Department of Conservation Sciences, Hazara University, Mansehra 21300, Pakistan.
⁶ Atta-ur-Rahman Institute for Natural Products Discovery (AuRIns), Universiti Teknologi MARA Cawangan Selangor Kampus Puncak Alam, 42300 Bandar Puncak Alam, Selangor D. E., Malaysia; Faculty of Pharmacy, Universiti Teknologi MARA Cawangan Selangor Kampus Puncak Alam, 42300 Bandar Puncak Alam, Selangor D. E., Malaysia.
⁷ Chemistry Department, King Fahd University of Petroleum and Minerals, Dhahran 31261, Saudi Arabia.
⁸ Department of Computer Information Systems, College of Computer Science & Information Technology (CCSIT), Imam Abdulrahman Bin Faisal University, P.O. Box 1982, Dammam 31441, Saudi Arabia.

PMID: 31176853
DOI: 10.1016/j.bioorg.2019.103024

Abstract

Despite of many diverse biological activities exhibited by benzimidazole scaffold, it is rarely explored for the urease inhibitory potential. For that purpose, benzimidazole analogues 1-19 were synthesized and screened for in vitro urease inhibitory potential. Structures of all synthetic analogues were deduced by different spectroscopic techniques. All analogues revealed inhibition potential with IC₅₀ values of 0.90 ± 0.01 to 35.20 ± 1.10 μM, when compared with the standard thiourea (IC₅₀ = 21.40 ± 0.21 μM). Limited SAR suggested that the variations in the inhibitory potentials of the analogues are the result of different substitutions on phenyl ring. In order to rationalize the binding interactions of most active compounds with the active site of urease enzyme, molecular docking study was conducted.

Keywords: Benzimidazole; Molecular docking; SAR; Synthesis; Urease inhibitory potential.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Benzimidazoles / chemical synthesis
Benzimidazoles / chemistry
Benzimidazoles / pharmacology*
Dose-Response Relationship, Drug
Enzyme Inhibitors / chemical synthesis
Enzyme Inhibitors / chemistry
Enzyme Inhibitors / pharmacology*
Molecular Docking Simulation*
Molecular Structure
Structure-Activity Relationship
Urease / antagonists & inhibitors*
Urease / metabolism

Substances

Benzimidazoles
Enzyme Inhibitors
Urease