Issue 54, 2020

Pharmacoinformatics approaches to identify potential hits against tetraacyldisaccharide 4′-kinase (LpxK) of Pseudomonas aeruginosa

Abstract

Pseudomonas aeruginosa infection can cause pneumonia and urinary tract infection and the management of Pseudomonas aeruginosa infection is critical in multidrug resistance, hospital-acquired bacteremia and ventilator-associated pneumonia. The key enzymes of lipid A biosynthesis in Pseudomonas aeruginosa are promising drug targets. However, the enzyme tetraacyldisaccharide 4′-kinase (LpxK) has not been explored as a drug target so far. Several pharmacoinformatics tools such as comparative metabolic pathway analysis (Metacyc), data mining from a database of essential genes (DEG), homology modeling, molecular docking, pharmacophore based virtual screening, ADMET prediction and molecular dynamics simulation were used in identifying novel lead compounds against this target. The top virtual hits STOCK6S-33288, 43621, 39892, 37164 and 35740 may serve as the templates for the design and synthesis of potent LpxK inhibitors in the management of serious Pseudomonas aeruginosa infection.

Graphical abstract: Pharmacoinformatics approaches to identify potential hits against tetraacyldisaccharide 4′-kinase (LpxK) of Pseudomonas aeruginosa

Article information

Article type
Paper
Submitted
02 Aug. 2020
Accepted
24 Aug. 2020
First published
04 Sept. 2020
This article is Open Access
Creative Commons BY-NC license

RSC Adv., 2020,10, 32856-32874

Pharmacoinformatics approaches to identify potential hits against tetraacyldisaccharide 4′-kinase (LpxK) of Pseudomonas aeruginosa

M. G. Damale, S. K. Pathan, R. B. Patil and J. N. Sangshetti, RSC Adv., 2020, 10, 32856 DOI: 10.1039/D0RA06675C

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