Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

Exploring the action of new FimH inhibitors against CTX–15 enzyme by enzoinformatics approach: A plausible arsenal against drug-resistant uropathogenic bacterial strains

Amir Saeed^1,2 , Khalid Alshaghdali^1,3, Mohd Saeed³, Mousa Alreshidi^3,4

¹Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, University of Hail, Hail, Saudi Arabia; ²Department of Medical Microbiology Faculty of Medical Laboratory Sciences, University of Medical Sciences and Technology, Khartoum, Sudan; ³Molecular Diagnostic and Personalized Therapeutic Unit, University of Hail, Hail, Saudi Arabia; ⁴Department of Biology, College of Sciences, University of Hail, Hail, Saudi Arabia.

For correspondence:- Amir Saeed Email: am.saeed@uoh.edu.sa Tel:+966543099741

Accepted: 6 October 2021 Published: 30 November 2021

Citation: Saeed A, Alshaghdali K, Saeed M, Alreshidi M. Exploring the action of new FimH inhibitors against CTX–15 enzyme by enzoinformatics approach: A plausible arsenal against drug-resistant uropathogenic bacterial strains. Trop J Pharm Res 2021; 20(11):2363-2370 doi: 10.4314/tjpr.v20i11.19

© 2021 The authors.
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Abstract

Purpose: To explore the potency of FimH inhibitors against CTX-M β-lactamase enzyme type 15, in view of the increasing prevalence of CTX-M 15 in uropathogenic strains which has reduced the treatment options to minimal.

Method: FimH inhibitors were targeted against CTXM-15 by a molecular docking approach. Thereafter, the best ligand-target confirmation was selected and analyzed using LIGPLOT+ Version v.2.1. The hydrophobic and hydrogen bonding among the catalytic site amino acids of CTXM-15 and the FimH inhibitors were analyzed and 3-D structures were converted into 2-D images by LIGPLOT algorithm.

Results: Out of all the FimH inhibitors tested, 3′-chloro-4′- (α-D-mannopyranosyloxy) biphenyl-4-carbonitrile, para-biphenyl-2-methyl-3′-methylamidemannoside, para-biphenyl-2-methyl-3′,5′di-methylamide-α-D-mannoside, and thiazolylamino mannoside exhibited better interaction with the CTX-M 15 active site than the positive control avibactam. Moreover, in CTX-M 15, the amino acid residues, Ser70, Tyr105, Ser130, Asn132, Thr216, Thr235, Gly236, and Ser237 were commonly interacting with these FimH inhibitors as well as avibactam.

Conclusion: The predicted findings suggest that these FimH inhibitors could be explored as potential CTX-M 15 inhibitors to cope-up with resistance issues of uropathogenic bacteria in the form of an alternate strategy.

Keywords: Antibiotic resistance, CTX-M 15 enzyme, Extended-spectrum ?-lactamases, FimH, Urinary tract infections, Uropathogenic bacteria