Synthesis and characterization of a novel Mannich base benzimidazole derivative to explore interaction with human serum albumin and antimicrobial property: experimental and theoretical approach

Abstract

The novel Mannich base benzimidazole derivative (CB-1), 1-((1H-benzo[d]imidazol-1-yl)(3-chlorophenyl)methyl)-3-phenylurea) has been designed and synthesized by reacting benzimidazole, 3-chloro benzaldehyde, and N-Phenyl urea. CB-1 has been characterized by UV- Visible, FTIR, and ¹H NMR. CB-1 was explored to study the interaction with the most abundant blood protein which involved in the role of transport of molecules (drugs), human serum albumin (HSA). Fluorescence results are evident for the presence of both dynamic and static quenching mechanisms in the binding of CB-1 to HSA. Antimicrobial screening were carried out against three bacteria and three fungi pathogens employing disc diffusion method. Molecular docking using AutoDock Vina tool further confirms the experimental binding interactions obtained from fluorescence. Density functional theory (DFT) with B3LYP/6-311G++ basis set was used for correlating theoretical data and obtaining optimized structures of CB-1 along with reactants with molecular electrostatic potential (MEP) map and HOMO→LUMO energy gap calculation.

HIGHLIGHTS

• The novel Mannich base benzimidazole derivative (CB-1) has been designed and synthesized by Mannich reaction.

• CB-1 has been characterized by UV- Visible, FTIR, and ¹H NMR.

• Fluorescence quenching reveals that HSA binds to CB-1 via aromatic residues, which is corroborated by molecular docking.

• Antifungal and antibacterial activity was evaluated in comparison to Nystatin and Gentamicin standard drugs, respectively.

• DFT calculations support experimental data and provide HOMO-LUMO energy gap.

Communicated by Ramaswamy H. Sarma

Keywords:

• Mannich reaction
• benzimidazole derivative
• human serum albumin
• antimicrobial activity
• molecular docking
• DFT

Acknowledgment

Thanks to Jamal Mohamed College Management and Principal for the necessary facilities provided for research. Also thanks to Dr. Ishaat M. Khan, Department of Chemistry, AMU, Aligarh, for the guidance.

Disclosure statement

No potential conflict of interest was reported by the authors.

Funding

The author(s) reported there is no funding associated with the work featured in this article.