Design and synthesis of tetrahydrochromeno[3,4-e]isoindole-1,3(2H,3aH)-dione derivatives via the Diels–Alder reaction: molecular docking, antibacterial activity, ADMET analysis and photophysical properties

Abstract

A series of fused tetrahydrochromeno[3,4-e]isoindole-1,3(2H,3aH)-dione derivatives was successfully synthesized via the Diels–Alder reaction. Molecular docking studies were conducted to understand the interaction modes between the synthesized hybrid compounds and the receptor bacterial strains of Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). Notably, the in silico results demonstrated that compound 19l (−8.7 kcal mol⁻¹ with E. coli and −8.4 kcal mol⁻¹ with S. aureus) and 19p (−8.7 kcal mol⁻¹ with E. coli and −9.1 kcal mol⁻¹ with S. aureus) exhibited good binding values. Additionally, the in vitro antibacterial studies showed that compounds 19l and 19p demonstrated excellent antibacterial activities, with a zone of inhibition (ZI) of 17 mm and a minimum inhibitory concentration (MIC) of 12.5 μg mL⁻¹ against both E. coli and S. aureus, which were comparable to the performance of the standard antibiotic ciprofloxacin. Further, the bioavailability was assessed through virtual ADMET parameters, which suggested that most of the compounds possessed favorable pharmacokinetic profiles. To further enrich the study, photophysical properties of all the synthesized molecules were also examined using UV-visible and fluorescent spectroscopies.