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Scientific article
English

Blood schizontocidal activity of selected 1,2,4-trioxanes (Fenozans) against the multidrug-resistant strain of Plasmodium yoelii nigeriensis (MDR) in vivo

Published inParasitology, vol. 133, no. 1, p. 1-9
Publication date2006
Abstract

Blood schizontocidal activity of 10 selected cis-fused cyclopenteno-1,2,4-trioxanes (namely Fenozan compound nos 6, 7, 11, 27, 32, 39, 44, 45, 48 and 51) have been re-investigated to establish their curative doses against the multidrug-resistant Plasmodium yoelii nigeriensis strain, which is lethal in Swiss mice. Freshly prepared formulations of these compounds prepared either in neutral groundnut (peanut) oil or in dimethyl sulfoxide (DMSO)-Tween-water, were compared for their antimalarial activity. Only 2 compounds, namely Fenozan derivatives 11 and 45, formulated in neutral groundnut oil for oral administration, showed highest activity with 100% cure rate in MDR P. yoelii nigeriensis-infected mice, while the DMSO-Tween-water formulations were inactive. Fenozan-48 produced 72.2% cure, when administered orally in groundnut oil (formulation) while its DMSO-Tween formulation was inactive. In the case of Fenozan 7, the oil and DMSO-Tween formulations produced 92.3 and 76.0% cures respectively. Fenozan derivatives nos 6, 27, 32, 39, 44 and 51 were not protective either in groundnut oil or DMSO-Tween oral formulations. The present study has applied more rigorous criteria for selection of active compounds, and has identified the 3,3-spirocyclopentane derivative Fenozan 11, and the 3,3-spirohydropyran derivative Fenozan 45, as potential blood schizontocides which can completely eliminate multidrug-resistant malaria infection in mice. Both these compounds are candidates for pre-clinical development. The present study advocates the preferred use of an oil vehicle for oral evaluation of potential antimalarial trioxanes/fenozans instead of the DMSO formulation, which gives inferior curative efficacy.

Keywords
  • Trioxanes
  • Fenozans
  • Antimalarials
  • Plasmodium yoelii nigeriensis
  • Multidrug resistant (MDR)
Citation (ISO format)
TRIPATHI, Renu, JEFFORD, Charles, DUTTA, Guru P. Blood schizontocidal activity of selected 1,2,4-trioxanes (Fenozans) against the multidrug-resistant strain of Plasmodium yoelii nigeriensis (MDR) in vivo. In: Parasitology, 2006, vol. 133, n° 1, p. 1–9. doi: 10.1017/S0031182006009905
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