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.