Chandrasekar K, Kumar B, Saravanan A, Victor A, Sivaraj S, Haridoss M, Priyadurairaj P, Hemalatha C. N, Muthukumar V. A. Evalution and Molecular Docking of Benzimidazole and its Derivatives as a Potent Antibacterial Agent. Biomed Pharmacol J 2019;12(4).

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Manuscript received on :06-03-2019
Manuscript accepted on :05-11-2019
Published online on: 13-12-2019

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Plagiarism Check: Yes
Reviewed by: Junir Antonio Lutinski
Second Review by: Reem A A
Final Approval by: Dr. Kishore Kumar Jella

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Kamatchi Chandrasekar¹*, Bhawani Kumar², Arunkumar Saravanan², Ayush Victor², Saranya Sivaraj², Magesh Haridoss², Priyadurairaj², Catna Nagaraj Hemalatha³ and Vijey Aanandhi Muthukumar³

¹Biotechnology Department, The Oxford College of Science (TOCS), Bangalore, Karnataka 560102, India

²Biotechnology Department, Dr.M.G.R Educational and Research Institute,Chennai Tamil Nadu-600095,India

³School of Pharmaceutical sciences Vels University (VISTAS)

Corresponding Author E-mail: ckamatchi@gmail.com

DOI : https://dx.doi.org/10.13005/bpj/1814

Abstract

The study was performed to identify a potent antibacterial benzimidazole derivative using in vitro and in silico techniques. Benzimidazole and its derivatives were synthesized by reflux process. The derivatives were screened for antibiotic susceptibility test (AST) and minimum inhibitory concentration (MIC) against Gram-negative and Gram-positive clinical isolates and compared with the positive control Norfloxacin. Insilico molecular docking was performed to screen the binding potential of the derivatives with target enzymes topoisomerase II /DNA gyraseof Escherichia coli (E.coli) and Staphylococcus aureus (S.aureus) along with the control Norfloxacin.Totally fifty-four isolates were screened for antimicrobial supectibility test (AST) and minimum inhibitory concentration (MIC) and 35 clinical isolates of Gram-negative showed 86% resistance to Norfloxacin and 19 isolates of Gram-positive showed 90% resistance to Norfloxacin.  However, these isolates were found to be sensitive to 1-(4-((1H–benzimidazol-1-yl) methylamino) phenyl) ethanone (3) (C2), and 2-methyl-1H-benzimidazole (C4) compounds, with MIC ranges from 6.25- 12.5 µg/ml. Molecular docking analysis revealed that the compound C2 exhibited better binding affinity towards topoisomerase II / DNA gyrase of E.coli and S.aureus when compared with C4 and control Norfloxacin. The antibacterial activity of these may due to the inactivation of these enzymes which is supported by the MIC results.The obtained in vitro and in silico results suggested that C2 showed better antimicrobial activity.

Keywords

Synthesis; Benzimidazole; 1-(4-((1H–benzimidazol-1-yl)methylamino)phenyl) ethanone (3); Antibacterial activity; Minimum inhibitory concentration; Molecular docking

Introduction

In recent years, the increased multidrug-resistant (MDR) bacteria have raised an alarm throughout the world.^1,2 Around 50% of the antimicrobial drugs prescribed for human diseases, found to be unnecessary³ .This use, misuse, overuse or over the counter has driven the major source towards the antimicrobial resistance⁴ .Thus usage of antibiotics has become the major cause for the emergence and spreading of multi-drug resistant isolates of a group of microorganisms.⁵

Gram-negative pathogens are predominantly troublesome since it has become resistant to all antibiotics that are in current use. The emergence of MDR (PAN resistance) in Gram-negative infectious occur in health care center commonly caused by Klebsiellapneumoniae, Pseudomonas aeruginosa, and Acinetobacterspecies.⁶ Among Gram-positive pathogens, S.aureus and Enterococcusspecies are the biggest threats.^7,8 Furthermore, the antimicrobial drugs are expensive and cause undesirable side effects. Therefore, in light of the evidence of rapid global spread of resistant clinical isolates, we are in need to find out the new antimicrobial agents for future use.

Even though the newer use of antibiotics possesses a different mode of action against emerging bacterial resistance strains, we are still in need of more effective and potent antimicrobials. In recent years, benzimidazole has gained more attention, as the ring is an important pharmacophore in modern drug discovery. Benzimidazole derivatives have been reported to possess various biological activities such as anti-cancer, anti-viral, anti-bacterial, anti-fungal, anti-helmintic, anti-inflammat