Amino- and fluoro-substituted quinoline-4-carboxylic acid derivatives: MWI synthesis, cytotoxic activity, apoptotic DNA fragmentation and molecular docking studies

摘要: In continuation of our research work on amino substituted quinoline-4-carboxylic acid derivatives, microwave irradiated and conventional heating methods were used for synthesis target compounds. Benzaldehyde, pyruvic acid, 3-chloro-4-fluoroaniline in absolute ethanol media reacted, condensed, cyclized to form intermediate 7-chloro-6-fluoro-2-phenyl-quinoline-4-carboxylic acid. This reacted with various amines attaining desired products 6-fluoro-2-phenyl-7-substitutedamino-quinoline-4-carboxylic derivatives (7a–7l). Products obtained by synthesizer showed short reaction time 110–210 s yield 91–96 %, demonstrating advantages the said method. All synthesized compounds identified characterized FT-IR, 1H 13C NMR, Mass spectroscopy, Elemental analysis. Synthesized tested their effect cellular viability against carcinoma cell lines viz. MCF-7, HELA, Hep-2, NCI, HEK-293, VERO XTT bioassay at 24 h drug exposure using doxorubicin methotrexate as standard drugs. Majority proved be more potent than 7a, 7c, 7d, 7i exhibited significant anticancer activity. Apoptotic DNA fragmentation was carried out MCF-7 HEK-293 found that few excellent pattern confirming apoptosis. Docking study performed Surflexdock establish probable mechanism action X-ray crystallographic structure ATPase domain hTopoIIα. experiments confirmed good correlation between calculated interactions hTopoIIα observed IC50 values. The present may considered promising lead future design inhibitors novel agents.