Repurposing Potential of Diminazene Aceturate as an Inhibitor of the E. coli DNA Gyrase B

Varsha Dwivedi; Archana Ayyagari; Rakhi Chandran; Prerna Diwan; Sanjay Gupta; Vandana Gupta*

Varsha Dwivedi, Archana Ayyagari, Rakhi Chandran, Prerna Diwan, Sanjay Gupta and Vandana Gupta*

Volume1-Issue6
Dates: Received: 2020-10-23 | Accepted: 2020-10-30 | Published: 2020-10-31
Pages: 263-270

Abstract

Drug-resistant Escherichia coli (E. coli) has overburdened the healthcare facilities in recent years and is getting hard to combat, mandating search for novel therapeutics with a broad antibacterial spectrum and high chemotherapeutic index. The 24 kDa domain of DNA gyrase B that is involved in the ATPase activity has been reported to be a promising target for inhibitors. A PDB structure (1KZN) of the 24kD domain of gyrase B with the co-crystallized ligand clorobiocin was used for the docking studies to explore a library of 2924 FDA approved drugs from www.zinc.docking.org. FlexX docking module from Biosolve IT was used for receptor preparation and in silico docking experiments. Docking studies on the pocket created around the reference ligand clorobiocin revealed the best score with diminazene aceturate and it also demonstrated interactions with the crucial amino acids present within the pocket. Diminazene aceturate has been conventionally been used as an antiparasitic molecule in animals and it has also been demonstrated to exhibit repurposing potential in the treatment of disorders triggered due to overproduction of inflammatory cytokines, pulmonary hypertension, ischemia-induced cardiac pathophysiology, etc. among others. Findings from this study indicate the possibility of repurposing the age-old molecule diminazene aceturate into a DNA gyrase B antagonist to combat not just the drug-resistant E. coli but also other gram-negative ESKAPE pathogens. It may also aid in alleviating the inflammatory response induced in the body of the patients suffering from septicemia caused by a variety of Gram-negative bacterial pathogens.

FullText HTML FullText PDF DOI: 10.37871/jbres1153

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How to cite this article

Dwivedi V, Ayyagari A, Chandran R, Diwan P, Gupta S, Gupta V. Repurposing Potential of Diminazene Aceturate as an Inhibitor of the E. coli DNA Gyrase B. J Biomed Res Environ Sci. 2020 Oct 31; 1(6): 263-270. doi: 10.37871/jbres1153, Article ID: jbres1153

Subject area(s)

Therapeutics

Pharmacology

University/Institute

University of Delhi

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