Synthesis, molecular docking, ADME study, and antimicrobial potency of piperazine based cinnamic acid bearing coumarin moieties as a DNA gyrase inhibitor

Abstract

A series of novel piperazine based cinnamic acid bearing coumarin derivatives were designed and synthesized by piperazine based cinnamic acids esterification with 4‐hydroxycoumarin and characterized by various spectral techniques like infrared, 1H nuclear magnetic resonance (NMR), 13C NMR, and mass. The novel bioactive compounds (7a‐7m) screen their potential against different bacterial and fungal strains. Compound 7g (minimum inhibitory concentration [MIC] = 12.5 µg/ml) exhibited potent antibacterial activity against Escherichia coli strain. Compounds 7d, 7f, 7g, 7k, 7l, and 7m showed potent antibacterial activity against all bacterial strains. Compounds 7a, 7g, 7h, 7k, 7l, and 7m exhibited potent antifungal activity against all fungal strains. Furthermore, a molecular docking study revealed that compounds 7d, 7f, 7g, and 7k could bind to the active site of E. coli DNA gyrase subunit B protein and form hydrogen bonding with crucial amino acid residues Arg136 in the active sites. Comprehensively, our study recommends that 7d, 7f, 7g, and 7k could be a promising lead for developing more efficient antimicrobial drug candidates and DNA gyrase inhibitors.

Versatile Therapeutic Values of N‐Containing Heterocycles Benzimidazole, Piperazine and Piperidine Hybrids

“…Compound 25 exhibited significant antibacterial activity against Escherichia Coli strain with MIC of 12.5 μg/mL. Additionally, ADME and molecular docking studies revealed that compound 25 binds to active amino acid residues of the DNA gyrase protein [74,75] …”

“…Additionally, ADME and molecular docking studies revealed that compound 25 binds to active amino acid residues of the DNA gyrase protein. [74,75] Piperidine-linked triazole hybrids designed and developed by Zhigan et al were evaluated for antifungal activity. Compound 26 exhibited significant activity against candida albicans with a MIC of 0.0125 μg/mL and Cryptococcus neoformans with a MIC of 0.125 μg/mL.…”