In silico studies-assisted design, synthesis, and discovery of biologically active isatin derivatives

Purpose: To design isatin-based compounds, carry out in silico studies, and identify the biologically active isatin derivatives. Methods: Fourteen isatin-based compounds (A to N) were designed using ChemDraw. In addition, in silico studies (molecular docking, prediction of drug likeliness, gastrointestinal absorption, log P, and toxicity) of the designed compounds were compared to ciprofloxacin. Based on the results of the in silico studies, three compounds (G, H, and L) were selected for synthesis, and the chemical structures of G, H, and L were elucidated via spectral analysis. The antimicrobial activity and DNA gyrase inhibitory activity of G, H, and L were evaluated and compared to those of ciprofloxacin. Results: The docking scores of compounds G, H, and L (-5.90, -5.72, and -5.98 kcal/mol, respectively) were comparatively better than that of ciprofloxacin (-5.41 kcal/mol). In silico studies data also revealed the non-hepatotoxic nature, drug-likeliness properties, and good gastrointestinal absorption for G, H, L, and ciprofloxacin. The in vitro antimicrobial activity (p < 0.05) and DNA gyrase inhibitory activity of G (102.33 %, p < 0.05), H (104.43 %, p < 0.05), and L (106.77 %, p < 0.05) were better than those of ciprofloxacin (100.0 %, p < 0.05). Conclusion: Compounds G, H, and L are promising DNA gyrase inhibitors. These compounds should be explored further to determine their broad-spectrum antimicrobial potency, safety, and efficacy.

Automated summary

This study designed 14 isatin-based compounds and performed in silico studies to identify biologically active isatin derivatives. Three compounds (G, H, and L) showed promising antimicrobial activity and DNA gyrase inhibitory activity, suggesting their potential as broad-spectrum antimicrobial agents.