Synthesis, molecular modeling of N-acyl benzoazetinones and their docking simulation on fungal modeled target

ABSTRACT

A series of stable N-acyl benzoazetinones have been synthesized in moderate to good yields (58–85%) from easily available substrates such as 2-(N-acyl) amino benzoic acids through intramolecular amidation under mild conditions. These geometry-optimized benzoazetinones were docked in the model target of P450, class CYP53A15, a benzoate 4-monooxygenase abundantly found in the genome of ascomycetes and Basidiomycetes classes of pathogenic fungi. Low per residue root-mean-square deviation (RMSD) of modeled structure of the enzyme indicated similar topology as template (4D6Z.pdb). Observed score judges site-specific docking, and the interaction of quantum mechanically optimized benzoazetinone derivatives with the target enzyme. These results suggest that 3i is the best antifungal agent. The specific hydrophobic substituent in the benzoazetinones contributed to the stability of ligand–target complex. Overall, the study provided insight into the specificity of the site-specific interactions, thereby, facilitating the possibility of development of broad-spectrum antifungal agents against opportunistic and infectious fungi.

GRAPHICAL ABSTRACT

KEYWORDS:

• 2-(N-acyl) amino benzoic acids
• EDC · HCl
• HOBt
• molecular docking
• molecular modeling
• N-acyl benzoazetinones

Acknowledgments

We thank UGC (New Delhi) for providing Shimadzu UV–Vis, FTIR and GCMS spectrometers. We also thank DST (New Delhi) for providing Bruker single crystal XRD and Thermo Scientific HRMS instruments under the DST–PURSE and DST–FIST programme, respectively. We (Inul Ansary and Arijit Das) are also grateful to The University of Burdwan for financial support under the University Level Research Assistance programme. Amal Kumar Bandyopadhyay likes to thank Professor Anirvan Misra, Department of Chemistry, North Bengal University, for allowing us to use his Gaussian software.