Abstract
Synthesis and evaluation of the antimalarial activity of new pyridine quinoline hybrid molecules against a chloroquine-susceptible strain of Plasmodium falciparum and as inhibitors of β-hematin formation are described. Two novel pyridine quinoline hybrid molecules and one bisquinoline molecule were synthesized and purified by column chromatography and evaluated for antimalarial and haem polymerization inhibition (HPIA) activities. The molecules were found to be very good haem polymerization inhibitors but showed poor antimalarial activity. This was attributed to their low vacuole accumulation ratio (VAR) in comparison to chloroquine. These molecules can be used as templates for designing new antimalarials targeting haem detoxification pathway of malaria parasite.
Graphical Abstract
Synthesis and antimalarial evaluation of novel pyridine quinoline hybrids
B.N Acharya, D. Thavaselvam# and M.P Kaushik*
Discovery Centre, Process Technology Development Division
Defence R & D Establishment, Jhansi Road, Gwalior-474002 (MP) INDIA
#Division of Microbiology, Defence Research and Development Establishment,Gwalior-474002, India
Synthesis and evaluation of antimalarial activity of new pyridine–quinoline hybrid molecules against a chloroquine-susceptible strain of Plasmodium falciparum and as inhibitors of β-hematin formation are described.
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Acknowledgements
We thank Dr. R. Vijayaraghavan, Director DRDE, Gwalior for his keen interest and encouragement in the present work. We especially thank Mr. Avik Mazumdar and Mr. Basant Lal for NMR analysis and Mr. Asish K. Srivastav for FTIR and ESI-MS analysis.
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Narayan Acharya, B., Thavaselvam, D. & Parshad Kaushik, M. Synthesis and antimalarial evaluation of novel pyridine quinoline hybrids. Med Chem Res 17, 487–494 (2008). https://doi.org/10.1007/s00044-008-9092-5
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DOI: https://doi.org/10.1007/s00044-008-9092-5