1. A novel 8-nitro quinoline-thiosemicarbazone analogues induces G1/SG2/M phase cell cycle arrest and apoptosis through ROS mediated mitochondrial pathway
- Author
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Raju Vivek, Thangaraj Arasakumar, Thangaraj Suresh, Palathurai Subramaniam Mohan, Shunmuganarayanan Athimoolam, Selvaraj Shyamsivappan, and Arjunan Saravanan
- Subjects
Models, Molecular ,Thiosemicarbazones ,Programmed cell death ,Cell cycle checkpoint ,Mice, Nude ,Uterine Cervical Neoplasms ,Antineoplastic Agents ,Apoptosis ,Breast Neoplasms ,Crystallography, X-Ray ,01 natural sciences ,Biochemistry ,Cell Line, Tumor ,Drug Discovery ,Animals ,Humans ,MTT assay ,Molecular Biology ,Mice, Inbred BALB C ,010405 organic chemistry ,Chemistry ,Organic Chemistry ,Cell Cycle Checkpoints ,Molecular biology ,0104 chemical sciences ,Mitochondria ,Molecular Docking Simulation ,010404 medicinal & biomolecular chemistry ,Intrinsic apoptotic signaling pathway ,Cell culture ,Cancer cell ,Quinolines ,Female ,Reactive Oxygen Species ,Estrogen receptor alpha - Abstract
A series of novel 8-nitro quinoline-based thiosemicarbazone analogues were synthesized and characterized by various spectroscopic and single crystal X-ray analyses. The potent antitumor effects of synthesized compounds towards the cancer cells were evaluated by MTT assay. Amongst, the compound 3a exhibited the highest inhibitory activity and the compounds 3f and 3b were also showed significant activity. The molecular mechanistic studies of cell death have demonstrated that the treated potent compound 3a induced G1/S & G2/M phase cell cycle arrest and induced apoptosis via mitochondrial dysfunction and increased the production of cytotoxic ROS levels. The RT-PCR gene expression analysis revealed that the cell death induced by activation of caspase-3 dependent intrinsic apoptotic signaling pathway. Further, the molecular binding affinity of compounds with estrogen receptor alpha was calculated by molecular docking studies. Thus, novel 8-nitro quinoline-thiosemicarbazone analogues provide a unique tool for breast cancer therapeutic tactics.
- Published
- 2020