Nandakumar Vandana, Sundarasamy Amsaveni, Adhigaman Kaviyarasu, Ramasamy Sentamil Selvi, Paulpandi Manickam, Kodiveri Muthukaliannan Gothandam, Narayanasamy Arul, Thangaraj Suresh
School of Chemical Sciences, Department of Chemistry, Bharathiar University Coimbatore Tamil Nadu 641046 India
Disease Proteomics laboratory, School of Life Sciences, Department of Zoology, Bharathiar University Coimbatore Tamil Nadu 641046 India.
RSC Med Chem. 2023 May 17;14(7):1331-1343. doi: 10.1039/d3md00165b. eCollection 2023 Jul 20.
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 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 μM. 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.
合成了一系列新型的基于8-硝基喹啉酮的芳香杂环酰腙，并通过各种光谱技术对其进行了表征。对它们与非小细胞肺癌细胞系A549凋亡相关的各种蛋白质进行了分子对接的理论研究。结果表明，所有合成化合物的可能相互作用模式都适合用作抗增殖药物。此外，通过理论ADMET分析研究了这些化合物的类药性质，结果表明它们具有良好的胃肠道吸收以及低毒性。通过MTT法使用A549、MCF-7和HeLa细胞系对所选化合物的抗癌活性进行了评估，以确定细胞毒性。化合物3c、3a和11c对A549细胞表现出显著的细胞毒性，顺序为3c（15.3±0.7）>3a（15.8±0.1）>11c（17.1±0.2），而所有化合物在浓度高达200μM时对正常人胚肾细胞均无明显毒性。选择该系列中最佳的化合物（3c和11c），通过使用AO/EtBr和DAPI的荧光显微镜技术进一步检测细胞凋亡。还通过流式细胞术研究了细胞周期中DNA合成的减少情况。结果表明，这些化合物由于激活了线粒体介导的内在途径而具有显著的抗癌特性。
