A Synthetic Route Towards Spiro Indanone Fused Pyrano[2,3‐c]Chromene Derivatives via Oxa–Diels–Alder Reaction: Computational Investigation, Antibacterial Evaluation and Molecular Docking Studies as Potential DNA Gyrase Inhibitors

Abstract

A highly efficient method for the synthesis of 2′H‐spiro[indene‐2,3′‐pyrano[2,3‐c]chromene] derivatives 20(a–s) has been developed involving oxa–Diels–Alder reaction as the key step under conventional conditions in good to excellent yields. The compounds were all characterized using 1H, 13C NMR, HRMS, and X‐ray crystallography. The present study employs DFT to validate the reaction pathway. In vitro antibacterial assay of all the synthesized derivatives was evaluated against Gram‐negative Escherichia coli and Gram‐positive Staphylococcus aureus bacterial strains. Compound 20e was found to be the most potent molecule with ZI of 19 mm and MIC of 16 μg mL−1 in E. coli and ZI of 14 mm and MIC of 32 μg mL−1 in S. aureus. Additionally, 20e demonstrated a strong inhibition of DNA gyrase in silico, with a binding affinity of −9.3 and − 9.0 kcal/mol in E. coli and S. aureus respectively. Also, significant pharmacokinetic, physicochemical, and drug‐like properties of the spirocyclic compounds were further corroborated by ADME investigations. Hence, these new series of spiro indanone fused pyrano[2,3‐c]chromene derivatives may be potent druggable antibacterial agents in future.