In the search for solutions to the global health threat posed by antimicrobial resistance, the development of new compounds is crucial. In this context, the in vitro testing of known indolizinoquinolinedione analogs 1–7 revealed that N,N-syn regioisomers are more active than N,N-anti regioisomers. In particular, compound 2 (ethyl 5,12-dihydro-5,12-dioxoindolizino2,3-gquinoline-6-carboxylate) exhibited the most significant activity against Bacillus subtilis, B. cereus, Staphylococcus aureus, and methicillin-resistant S. aureus (MRSA) bacteria. The reported increased bioactivity of metal complexes and their ability to overcome drug resistance through metal coordination have induced the study of new metal complexes of compound 2. FT-IR spectroscopy combined with DFT-simulated spectra confirmed the C=O chelation in all Zn, Cu, and Mn complexes 8–10. ESI-MS isotopic cluster analysis and UV-Vis-derived Job’s plot provided significant evidence for 1:1 chelation. Finally, 1H NMR data were correlated to the DFT-calculated charge distribution. Complexes 8–10 displayed similar activity against B. subtilis, although this was lower than that for 2, and there were comparable effects with 2 and vancomycin antibiotic against S. aureus. FTsZ protein as a potential target of B. subtilis and DNA gyrase of S. aureus and MRSA were studied by docking calculations, revealing a good correlation with the in vitro results.
Vigna et al. (Mon,) studied this question.