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

Abstract

Abstract 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 IC 50 value of 10.38 µM and a MIC value of 6.25 µM. Conclusively, a density functional theory (DFT) calculation was studied.