Potent antibacterial activity of dihydydropyrimidine‐1, 3, 5‐triazines via inhibition of DNA gyrase and antifungal activity with favourable metabolic profile. (5th May 2020)

• Record Type: Journal Article
• Authors: Masih, Anup; Shrivastava, Jitendra Kumar; Bhat, Hans Raj; Singh, Udaya Pratap
• Is Part Of: Chemical biology & drug design. Volume 96:Number 2(2020)
• Page Start: 861
• Page End: 869
• Publication Date: 2020-05-05
• Subjects: 1, 3, 5‐triazine -- antibacterial -- antibiofilm -- DNA gyrase inhibition -- metabolic prediction; Drugs -- Design -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; 615.19005
• DOI: 10.1111/cbdd.13695
• Languages: English
• ISSNs: 1747-0277

Abstract

Abstract: The compounds were tested against panel of three Gram‐positive, viz. Staphylococcus aureus, Bacillus subtilis, Bacillus cereus and three Gram‐negative bacterial strains viz. Pseudomonas aeruginosa, Escherichia coli, and Proteus vulgaris where they showed significant to moderate antibacterial activity. The compound also showed considerable antibiofilm activity against S. aureus and B. subtilis . The most potent compounds 7l and 7m found bacteriostatic in time‐kill assay via inhibition of DNA gyrase enzyme and interacting with Glu58, Val130, Ile175 and Ile186 via numerous H‐bonds as revealed by docking. In S. aureus ‐induced murine infection model, compound 7m showed dose‐dependent reduction of viability of bacteria with maximum activity in 25 mg/kg treated group. The antifungal activity against human fungal pathogens was also estimated, where these compounds showed considerable inhibitory activity as compared to standard. The metabolic liability of compound 7m was determined using RS‐Predictor and MetaPrint 2D React. The molecules were proved as effective antibacterial agent via inhibition of DNA gyrase as a mechanism together with significant antifungal activity. Abstract : Various hybrid dihydydropyrimidine‐1, 3, 5‐triazines derivatives were developed as antibacterial and antifungal agents. The most promising antibacterial compounds, 7l and 7m, showed to inhibit S. aureus DNA gyrase enzyme with potent antibacterial activity against murine S. aureus infection model. The compounds also showed considerable antifungal activity against human fungal pathogens.