Synthesis, density functional theory (DFT) studies and urease inhibition activity of chiral benzimidazoles

Hasil Aman; Naghmana Rashid; Zaman Ashraf; Aamna Bibi; Hsin-Tsung Chen; Nadaraj Sathishkumar

doi:10.1016/j.heliyon.2020.e05187

Synthesis, density functional theory (DFT) studies and urease inhibition activity of chiral benzimidazoles

Heliyon. 2020 Oct 14;6(10):e05187. doi: 10.1016/j.heliyon.2020.e05187. eCollection 2020 Oct.

Authors

Hasil Aman^{1

2}, Naghmana Rashid¹, Zaman Ashraf¹, Aamna Bibi², Hsin-Tsung Chen², Nadaraj Sathishkumar²

Affiliations

¹ Department of Chemistry, Faculty of Science, Alama Iqbal Open University, Islamabad 44000, Pakistan.
² Department of Chemistry, School of Science, Chung Yuan Christian University, Taoyuan 32023, Taiwan.

Abstract

A variety of benzimidazole by the heterocyclization of orthophenylenediamine were synthesized in 69-86% yields. The synthesized compounds 3a-f and 6a-f were characterized and further investigated as jack bean urease inhibitors. Density functional theory (DFT) studies were performed utilizing the basis set B3LYP/6-31G (d, p) to acquire perception into their structural properties. Frontier molecular orbital (FMO) analysis of all compounds 3a-f and 6a-f was computed at the same level of theory to get a notion about their chemical reactivity and stability. The mapping of the molecular electrostatic potential (MEP) over the entire stabilized molecular geometry indicated the reactive centers. They exhibited urease inhibition activity with IC50 between 22 and 99 μM. Compounds containing withdrawing groups on the benzene ring (3d, 6d) were not showing significant urease inhibition. The value obtained for 3a, 3b, 3f had shown their significant urease inhibition for both theoretical and experimental. Notably, the compound having S-configuration (3a) (22.26 ± 6.2 μM) was good as compared to its R enantiomer 3f (31.42 ± 23.3 μM). Despite this, we elaborated the computational studies of the corresponding compounds, to highlight electronic effect which include HOMO, LUMO, Molecular electrostatic potential (MEP) and molecular docking.

Keywords: Benzimidazole; Density functional theory; HOMO; LUMO; Molecular docking; Organic chemistry; Pharmaceutical chemistry; Theoretical chemistry; Urease inhibition.