Rational design, synthesis of some quinolinone-Schiff bases/ pyridazino[4,5-c]quinolinones with potent anti-lung cancer and antituberculosis performance

This study reports the synthesis of binary and fused polycyclic hybrids based on quinolinone through the reaction of 3-acetyl-4-hydroxy-1-phenylquinolinone (AHQ) 1 with different amine and hydrazine derivatives to give corresponding Schiff bases 2-6 and hydrazones 8,9a-c. Whereas, formylation of hydrazone 9a, afforded pyrazolylquinolinone carbaldehyde 10. In addition, angular tricyclic systems 14-19 were synthesized from the reaction of hydrazone 8 with different aldehydes involving piperonal, chloroquinoline-3-carbaldehyde, chromene-3-carbaldehyde, ferrocenecarboxaldehyde, glyoxal and terephthalaldehyde. Whereas, the treatment of hydrazone 8 with different ketones afforded the corresponding bis-hydrazones 20-22 instead of the pyridazino skeletons. As well, all the synthesized hybrids were screened for their potential in vitro anti-lung cancer and antituberculosis activities (A549) and H37Rv strains, respectively. The molecular docking studies showed various strong π and hydrogen interactions with the newly synthesized quinolinone scaffolds. Interestingly, compounds 15, 16, and 19 manifested superior activity against both A549 and H37Rv. Interestingly, the most potent compound was 15 with an IC₅₀ value of 10.38 µM and a MIC value of 6.25 µM. Conclusively, a density functional theory (DFT) calculation was studied.