Indolyl‐4H‐Chromene Derivatives as Antibacterial Agents: Synthesis, in Vitro and in Silico Studies

Abstract In this study, indolyl‐4 H ‐chromene derivatives are designed and synthesised using an eco‐friendly multicomponent one‐pot synthesis using benzaldehydes, nitroketene N , S ‐acetals, and indoles combine with InCl 3 , a Lewis acid catalyst, and ethanol, an environmentally acceptable solvent. Due to antibiotic resistance, assessed these Indolyl‐4 H ‐chromene derivatives for their in vitro antibacterial activity against Gram‐positive and Gram‐negative bacteria, including Streptococcus pyogenes , Staphylococcus aureus , Clostridium pyrogenes , Bacillus subtilis , Escherichia coli , and Pseudomonas aeruginosa , using the agar well diffusion method and Minimum Inhibition Concentration (MIC) assay. Three compounds, 4‐(1 H ‐indol‐3‐yl)‐6‐methoxy‐ N ‐methyl‐3‐nitro‐4 H ‐chromen‐2‐amine, 4‐(1 H ‐indol‐3‐yl)‐3‐nitro‐ N ‐phenyl‐4 H ‐chromen‐2‐amine and 4‐(6‐Fluoro‐1 H ‐Indol‐3‐yl)‐ N ‐methyl‐3‐nitro‐4 H ‐chromen‐2‐amine showed better zone of inhibition (mm) and Minimum Inhibition Concentration (MIC) values of 10 μg/mL to 25 μg/mL against all bacterial types. The K i values of 278.60 nM and 2.21 nM for compound 4‐(1 H ‐indol‐3‐yl)‐3‐nitro‐ N ‐phenyl‐4 H ‐chromen‐2‐amine showed improved interactions with DNA gyrase B and topoIV ParE′s ATP binding sites in in silico studies.