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Antimicrobial Agents and Chemotherapy, October 2004, p. 3711-3714, Vol. 48, No. 10
0066-4804/04/$08.00+0     DOI: 10.1128/AAC.48.10.3711-3714.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

In Vitro Activities of 2,4-Diaminoquinazoline and 2,4-Diaminopteridine Derivatives against Plasmodium falciparum

Sheila Ommeh,1 Eunice Nduati,1 Eddy Mberu,1 Gilbert Kokwaro,1 Kevin Marsh,2,3 Andre Rosowsky,4 and Alexis Nzila1,5*

Kenya Medical Research Institute/Wellcome Trust Collaborative Research Program, Wellcome Trust Research Laboratories, Nairobi,1 Kenya Medical Research Institute/Wellcome Trust Collaborative Research Program, Centre for Geographical Medicine Research, Kenya Medical Research Institute, Kilifi Kenya,2 Nuffield Department of Medicine, John Radcliffe Hospital, Oxford,3 Department of Pharmacology and Therapeutics, University of Liverpool, Liverpool United Kingdom,5 Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts4

Received 17 December 2003/ Returned for modification 25 March 2004/ Accepted 21 June 2004

The activities of 28 6-substituted 2,4-diaminoquinazolines, 2,4-diamino-5,6,7,8-tetrahydroquinazolines, and 2,4-diaminopteridines against Plasmodium falciparum were tested. The 50% inhibitory concentrations (IC50s) of six compounds were <50 nM, and the most potent compound was 2,4-diamino-5-chloro-6-[N-(2,5-dimethoxybenzyl)amino]quinazoline (compound 1), with an IC50 of 9 nM. The activity of compound 1 was potentiated by the dihydropteroate synthase inhibitor dapsone, an indication that these compounds are inhibitors of dihydrofolate reductase. Further studies are warranted to assess the therapeutic potential of this combination in vivo.

* Corresponding author. Mailing address: Kenya Medical Research Institute (KEMRI)/Wellcome Trust Collaborative Research Program, Wellcome Trust Research Laboratories, P.O. Box 43640 GPO, 00100 Nairobi, Kenya. Phone: 254-2-2710672. Fax: 254-2-2711673. E-mail: anzila{at}wtnairobi.mimcom.net.

Antimicrobial Agents and Chemotherapy, October 2004, p. 3711-3714, Vol. 48, No. 10
0066-4804/04/$08.00+0     DOI: 10.1128/AAC.48.10.3711-3714.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Masseno, V., Muriithi, S., Nzila, A. (2009). In Vitro Chemosensitization of Plasmodium falciparum to Antimalarials by Verapamil and Probenecid. Antimicrob. Agents Chemother. 53: 3131-3134 [Abstract] [Full Text]  
  • Nzila, A. (2006). The past, present and future of antifolates in the treatment of Plasmodium falciparum infection. J Antimicrob Chemother 57: 1043-1054 [Abstract] [Full Text]  


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