Synthesis of novel guttiferone A derivatives: in-vitro evaluation toward Plasmodium falciparum, Trypanosoma brucei and Leishmania donovani

  • Eur J Med Chem. 2013 Jul:65:284-94. doi: 10.1016/j.ejmech.2013.04.066.
Yann Fromentin  1 ,  Nicolas Gaboriaud-Kolar ,  Bruno Ndjakou Lenta ,  Jean Duplex Wansi ,  Didier Buisson ,  Elisabeth Mouray ,  Philippe Grellier ,  Philippe M Loiseau ,  Marie-Christine Lallemand ,  Sylvie Michel
Affiliations
  • 1. Laboratoire de Pharmacognosie, UMR CNRS 8638, Université Paris Descartes Sorbonne Paris Cité, 4 avenue de l'Observatoire, 75006 Paris, France.
PMID: 23727538 DOI: 10.1016/j.ejmech.2013.04.066
Abstract

The catechol pharmacomodulation of the natural product guttiferone A, isolated from the Symphonia globulifera tree, led to the semisynthesis of a collection of twenty derivatives. The ester and ether derivatives of guttiferone A were evaluated for their anti-plasmodial, trypanocidal and anti-leishmanial activities. Some compounds described below have shown potent antiparasitic activity against Plasmodium falciparum, Trypanosoma brucei and Leishmania donovani in a range from 1 to 5 μM. The evaluation of guttiferone A derivatives against VERO cells highlighted catechol modulations as an interesting tool to decrease the toxicity and keep the activity of this natural compound. The current study revealed new molecules as promising new antiparasitic drug candidates.

Keywords
Antiparasitic activities; Guttiferone A derivatives; Natural products; Semi-synthesis; Substitution on the catechol ring.