A novel 8-nitro quinoline-thiosemicarbazone analogues induces G1/S & G2/M phase cell cycle arrest and apoptosis through ROS mediated mitochondrial pathway.

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.

Synthesis and X-ray study of dispiro 8-nitroquinolone analogues and their cytotoxic properties against human cervical cancer HeLa cells.

A series of unique dispiro analogues containing an oxindole pyrrolidine 8-nitroquinolone hybrid has been obtained through a one-pot three-component 1,3-dipolar cycloaddition of azomethine ylides generated in situ from the condensation of isatins and benzylamine with (E)-3-arylidene-2,3-dihydro-8-nitro-4-quinolones. The structures of the newly synthesized compounds were characterized by using different spectroscopic techniques and by X-ray diffraction studies of their regio- and stereochemistry. All the synthesized compounds were screened for in vitro cytotoxic activity against the human cervical cancer cell line HeLa. The compounds have exhibited potent inhibition against human cervical cancer cells and insignificant toxicity to normal cells. The compounds 6d, 6a, 6h, 6b, and 6e induced apoptosis of HeLa cells, through ROS influx. The expression levels of proteins involved in the mitochondrion-related pathways were detected, and Western blot analysis showed that apoptosis occurred via activation of caspase-3.

Biologically active perspective synthesis of heteroannulated 8-nitroquinolines with green chemistry approach.

A new class of pyrazolo[4,3-c]quinoline (5a-i, 7a-b) and pyrano[3,2-c]quinoline (9a-i) derivatives were designed and synthesized in moderate to good yields by microwave conditions. To enhance the yield of pyrano[3,2-c]quinoline derivatives, multicomponent one-pot synthesis has been developed. The synthesized compounds were identified by spectral and elemental analyses. Compounds 9a and 9i showed good antibacterial activity against Gram-positive and Gram-negative bacterial strains. All of the new compounds exhibited weak to moderate antioxidant activity, compound 9d exerted significant antioxidant power. The cytotoxicity of these compounds were also evaluated against MCF-7 (breast) and A549 (Lung) cancer cell lines. Most of the compounds displayed moderate to good cytotoxic activity against these cell lines. Compound 9i was found to be significantly active in this assay and also induced cell death by apoptosis. Molecular docking studies were carried out using EGFR inhibitor in order to determine the molecular interactions.

Synthesis of first ever 4-quinolone-3-carboxylic acid-appended spirooxindole-pyrrolidine derivatives and their biological applications.

A series of 4-quinolone-3-carboxylic acid-containing spirooxindole-pyrrolidine derivatives was synthesized via multicomponent 1,3-dipolar cycloaddition reactions of azomethine ylides with new (E)-4-oxo-6-(3-phenyl-acryloyl)-1,4-dihydroquinoline-3-carboxylic acids in good yields with high regioselectivity. The cycloadducts were characterized by analytical and spectral data including [Formula: see text], [Formula: see text], 2D NMR and mass spectroscopy. The structure of one of the compounds (8a) was investigated theoretically by computational techniques. DFT studies support the proposed mechanism for this cycloaddition reaction. Furthermore, antibacterial activities of the new compounds were evaluated against Gram-positive and Gram-negative bacterial strains. Compounds 8f, 8m and 8p showed potent inhibition activities against selected bacteria. The in vitro cytotoxicity of spirooxindole derivatives (8a-r) was evaluated against MCF-7 breast cancer cell line. Among the various compounds tested, compound 8f [Formula: see text] showed significant cytotoxic activity compared to the standard drug doxorubicin [Formula: see text].