Design, synthesis, and biological evaluation of multifunctional dispiro chromeno-indenoquinoxaline hybrids as dual anticancer and antibacterial agents with metal-ion sensing ability

Abstract

We have developed for the first time an aqueous-mediated 1,3-dipolar cycloaddition between indenoquinoxaline-derived nitrones and structurally diverse 2H-chromenes for the efficient construction of dispiro-chromeno-indenoquinoxaline frameworks. The molecular structures of the synthesized compounds were fully characterized by ¹H and ¹³C NMR spectroscopy and high-resolution mass spectrometry, with the solid-state structure of a representative derivative unambiguously confirmed by single-crystal X-ray diffraction analysis. In vitro biological assays indicated that the compounds possess promising activity against both cancer cell lines and pathogenic bacterial strains. Notably, compound 21j exhibited potent cytotoxicity against MCF-7 breast cancer cells (IC₅₀ = 1.59 ± 0.11 µM). In antibacterial assays, compound 21k demonstrated enhanced activity against Escherichia coli, whereas compound 21b showed superior efficacy against Staphylococcus aureus, surpassing the standard drug gentamicin. Molecular docking studies supported these results, indicating strong binding affinities of compounds 21k and 21b toward bacterial DNA gyrase, with docking scores of −9.8 and −9.0 kcal mol⁻¹, respectively. Furthermore, the synthesized heterocycles displayed pronounced fluorescence responses upon coordination with Fe²⁺ and Pd²⁺ ions, highlighting their potential utility in biological and analytical sensing applications.