Synthesis, antiplasmodial activity and mechanistic studies of pyrimidine-5-carbonitrile and quinoline hybrids

  • Eur J Med Chem. 2015 Aug 28:101:52-62. doi: 10.1016/j.ejmech.2015.06.024.
Hardeep Kaur  1 ,  Jan Balzarini  2 ,  Carmen de Kock  3 ,  Peter J Smith  3 ,  Kelly Chibale  4 ,  Kamaljit Singh  5
Affiliations
  • 1. Department of Chemistry, UGC-Centre of Advance Study-II, Guru Nanak Dev University, Amritsar 143005, India.
  • 2. Rega Institute for Medical Research, KU Leuven, 10 Minderbroedersstraat, B-3000 Leuven, Belgium.
  • 3. Division of Pharmacology, Department of Medicine, University of Cape Town, Observatory 7925, South Africa.
  • 4. Department of Chemistry, South African Medical Research Council Drug Discovery and Development Research Unit, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Rondebosch 7701, South Africa.
  • 5. Department of Chemistry, UGC-Centre of Advance Study-II, Guru Nanak Dev University, Amritsar 143005, India. Electronic address: [email protected].
PMID: 26114811 DOI: 10.1016/j.ejmech.2015.06.024
Abstract

A series of hybrids comprising of 5-cyanopyrimidine and quinoline moiety were synthesized and tested for in vitro antiplasmodial activity against NF54 and Dd2 strains of Plasmodium falciparum. Hybrid bearing m-nitrophenyl substituent at C-4 of pyrimidine displayed the highest antiplasmodial activity [IC50 = 56 nM] against the CQ(R) (Dd2) strain, which is four-fold greater than CQ.

Keywords
4-Aminoquinoline; Antiplasmodial agents; Cytotoxic activity; Heme binding; Hybrid antimalarials; Pyrimidine.