Journal of Clinical & Experimental Pharmacology

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

World Congress on Pharmacology

July 20-22, 2015 Brisbane, Australia

Hardik G Bhatt

Posters-Accepted Abstracts: Clin Exp Pharmacol

Abstract:

Cancer is one of the leading causes of death worldwide and is ranked second after cardiovascular diseases. It is a complex and evolving disease with the formation of defects at multiple genetic steps in a cell. In continuation of our research work on amino substituted quinoline-4-carboxylic acid derivatives, microwave irradiated and conventional heating methods were used for synthesis of target compounds, 6-fluoro-2-phenyl-7-substituted amino-quinoline-4-carboxylic acid derivatives. Benzaldehyde, pyruvic acid, and 3-chloro-4-fluoroaniline in absolute ethanol media condensed, and cyclized to form intermediate 7-chloro-6-fluoro-2-phenyl-quinoline-4-carboxylic acid. This intermediate reacted with various substituted amines attaining desired products. Products obtained by microwave synthesizer showed short reaction time and good yield. All compounds were characterized by spectral and elemental analysis and were tested for effect on cellular viability against various carcinoma cell lines viz. MCF-7, HELA, Hep-2, NCI, HEK-293, and VERO by XTT bioassay at 24 h of drug exposure using doxorubicin and methotrexate as standard drugs. Majority of the compounds proved to be more potent than doxorubicin and few compounds exhibited significant anticancer activity. Apoptotic DNA fragmentation was carried out on MCF-7 and HEK-293 cell lines and found that few compounds exhibited excellent DNA fragmentation pattern confirming apoptosis. Docking study was performed by Surflexdock to establish probable mechanism of action of synthesized compounds using X-ray crystallographic structure of the ATPase domain of hTopoIIa. Docking experiments confirmed good correlation between calculated interactions with the hTopoIIa and the observed IC50 values. The present study of quinoline-4-carboxylic acid derivatives may be considered as promising lead for future design of potent hTopoIIa inhibitors as novel anticancer agents.