Anti-proliferative activity of nitroquinolone fused acylhydrazones as non-small cell human lung cancer agents

A new series of 8-nitroquinolone-based aromatic heterocyclic acyl hydrazones have been synthesised and characterised through various spectroscopic techniques. They were theoretically examined for molecular docking with various proteins related to the apoptosis of the non-small cell lung cancer cell line A549. The results indicate that the possible modes of interaction of all the synthesised compounds are compatible for use as anti-proliferative drugs. Also, the drug-likeness of the compounds was examined through theoretical ADMET analysis, which indicated good gastrointestinal absorption as well as low toxicity. Selected compounds were evaluated for their in vitro anti-cancer activity using A549, MCF-7 and HeLa cell lines through an MTT assay to determine cytotoxicity. Compounds 3c, 3a and 11c exhibited significant cytotoxicity towards A549 cells in the order of 3c (15.3 +/- 0.7) > 3a (15.8 +/- 0.1) > 11c (17.1 +/- 0.2), whereas all the compounds show insignificant toxicity on normal human embryonic kidney cells up to a concentration of 200 mu M. The best compounds among the series (3c and 11c) were chosen for further detection of apoptosis through fluorescence microscopic techniques using AO/EtBr and DAPI. The reduced DNA synthesis during the cell cycle was also investigated through flow cytometric techniques. The results indicate that the compounds possess significant anticancer properties due to the activation of the mitochondrial mediated intrinsic pathway.

Automated summary

A new series of 8-nitroquinolone-based aromatic heterocyclic acyl hydrazones were synthesized and characterized. They were examined for compatibility as anti-proliferative drugs through molecular docking with proteins related to apoptosis in non-small cell lung cancer. The compounds showed good drug-likeness and low toxicity. Selected compounds exhibited significant cytotoxicity towards A549 cells and showed no toxicity on normal human embryonic kidney cells. The best compounds were further tested for apoptosis detection and investigated for reduced DNA synthesis during the cell cycle.