2. Academic Validation
  3. Novel 4-aminoquinoline-pyrimidine based hybrids with improved in vitro and in vivo antimalarial activity

Novel 4-aminoquinoline-pyrimidine based hybrids with improved in vitro and in vivo antimalarial activity

  • ACS Med Chem Lett. 2012 Jun 10;3(7):555-9. doi: 10.1021/ml3000808.
Sunny Manohar 1,  U Chinna Rajesh 1,  Shabana I Khan 2,  Babu L Tekwani 2,  Diwan S Rawat 1
Affiliations

Affiliations

  • 1 Department of Chemistry, University of Delhi , Delhi-110007, India.
  • 2 National Center for Natural Products Research, Department of Pharmacognosy, and Department of Pharmacology, School of Pharmacy, University of Mississippi , Mississippi 38677, United States ; National Center for Natural Products Research, Department of Pharmacognosy, and Department of Pharmacology, School of Pharmacy, University of Mississippi , Mississippi 38677, United States.
PMID: 24900509 DOI: 10.1021/ml3000808
Abstract

A class of hybrid molecules consisting of 4-aminoquinoline and pyrimidine were synthesized and tested for antimalarial activity against both chloroquine (CQ)-sensitive (D6) and chloroquine (CQ)-resistant (W2) strains of Plasmodium falciparum through an in vitro assay. Eleven hybrids showed better antimalarial activity against both CQ-sensitive and CQ-resistant strains of P. falciparum in comparison to standard drug CQ. Four molecules were more potent (7-8-fold) than CQ in D6 strain, and eight molecules were found to be 5-25-fold more active against resistant strain (W2). Several compounds did not show any cytotoxicity up to a high concentration (60 μM), Others exhibited mild toxicities, but the selective index for the antimalarial activity was very high for most of these hybrids. Two compounds selected for in vivo evaluation have shown excellent activity (po) in a mouse model of Plasmodium berghei without any apparent toxicity. The X-ray crystal structure of one of the compounds was also determined.

Keywords

4-aminoquinoline; antimalarial; pyrimidine.

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