Substituted Benzimidazole Analogues as Potential α-Amylase Inhibitors and Radical Scavengers

Akinsola Adegboye Akande; Uzma Salar; Khalid Mohammed Khan; Shazia Syed; Sherifat Adeyinka Aboaba; Sridevi Chigurupati; Abdul Wadood; Muhammad Riaz; Muhammad Taha; Saurabh Bhatia; Kanwal; Shahbaz Shamim; Shahnaz Perveen

doi:10.1021/acsomega.1c03056

Substituted Benzimidazole Analogues as Potential α-Amylase Inhibitors and Radical Scavengers

ACS Omega. 2021 Aug 26;6(35):22726-22739. doi: 10.1021/acsomega.1c03056. eCollection 2021 Sep 7.

Authors

Affiliations

¹ H. E. J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan.
² Organic Unit, Chemistry Department, University of Ibadan, Ibadan 200132, Nigeria.
³ Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan.
⁴ Department of Clinical Pharmacy, Institute for Research and Medical Consultations (IRMC), Imam Abdulrahman Bin Faisal University, P.O. Box 1982, Dammam 31441, Saudi Arabia.
⁵ Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, Qassim University, Buraidah 52571, Saudi Arabia.
⁶ Department of Biochemistry, Computational Medicinal Chemistry Laboratory, UCSS, Abdul Wali Khan University, Mardan 23200, Pakistan.
⁷ Natural & Medical Sciences Research Center, University of Nizwa, P.O. Box 33, 616 Birkat Al Mauz, Nizwa, Oman.
⁸ PCSIR Laboratories Complex, Karachi, Shahrah-e-Dr. Salimuzzaman Siddiqui, Karachi 75280, Pakistan.

Abstract

Benzimidazole scaffolds are known to have a diverse range of biological activities and found to be antidiabetic and antioxidant. In this study, a variety of arylated benzimidazoles 1-31 were synthesized. Except for compounds 1, 6, 7, and 8, all are new derivatives. All compounds were screened for α-amylase inhibitory, 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), and 2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activities. In vitro screening results revealed that all molecules demonstrated significant α-amylase inhibition with IC₅₀ values of 1.86 ± 0.08 to 3.16 ± 0.31 μM as compared to standard acarbose (IC₅₀ = 1.46 ± 0.26 μM). However, compounds showed significant ABTS and DPPH radical scavenging potentials with IC₅₀ values in the range of 1.37 ± 0.21 to 4.00 ± 0.10 μM for ABTS and 1.36 ± 0.09 to 3.60 ± 0.20 μM for DPPH radical scavenging activities when compared to ascorbic acid with IC₅₀ values of 0.72 ± 0.21 and 0.73 ± 0.05 μM for ABTS and DPPH radical scavenging potentials, respectively. Structure-activity relationship (SAR) was established after critical analysis of varying substitution effects on α-amylase inhibitory and radical scavenging (ABTS and DPPH) potentials. However, molecular docking was also performed to figure out the active participation of different groups of synthetic molecules during binding with the active pocket of the α-amylase enzyme.