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Medicinal Chemistry Research

, Volume 24, Issue 4, pp 1662–1671 | Cite as

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

  • Hardik G. BhattEmail author
  • Yadvendra K. Agrawal
  • Manish J. Patel
Original Research

Abstract

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. Benzaldehyde, pyruvic acid, and 3-chloro-4-fluoroaniline in absolute ethanol media reacted, 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 6-fluoro-2-phenyl-7-substitutedamino-quinoline-4-carboxylic acid derivatives (7a–7l). Products obtained by microwave synthesizer showed short reaction time of 110–210 s and yield of 91–96 %, demonstrating advantages of the said method. All synthesized compounds were identified and characterized by FT-IR, 1H and 13C NMR, Mass spectroscopy, and Elemental analysis. Synthesized compounds were tested for their 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 compounds 7a, 7c, 7d, and 7i 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 hTopoIIα. Docking experiments confirmed good correlation between calculated interactions with the hTopoIIα 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 hTopoIIα inhibitors as novel anticancer agents.

Keywords

Quinoline-4-carboxylic acid Microwave irradiation Cytotoxic activity Apoptosis hTopoIIα Molecular docking 

Notes

Acknowledgments

H. G. Bhatt is thankful to Nirma University, Ahmedabad, India for providing necessary facilities to carry out the research work.

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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Hardik G. Bhatt
    • 1
    Email author
  • Yadvendra K. Agrawal
    • 2
  • Manish J. Patel
    • 3
  1. 1.Department of Pharmaceutical Chemistry, Institute of PharmacyNirma UniversityAhmedabadIndia
  2. 2.Institute of Research and DevelopmentGujarat Forensic Sciences UniversityGandhinagarIndia
  3. 3.S. K. Patel College of Pharmaceutical Education & ResearchMehsanaIndia

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