title: Synthesis of novel guttiferone A derivatives: in-vitro evaluation toward Plasmodium falciparum, Trypanosoma brucei and Leishmania donovani.
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.
authors.affiliation: Laboratoire de Pharmacognosie, UMR CNRS 8638, Université Paris Descartes Sorbonne Paris Cité, 4 avenue de l'Observatoire, 75006 Paris, France.
authors.forename: Yann
authors.initials: Y
authors.lastname: Fromentin
authors.forename: Nicolas
authors.initials: N
authors.lastname: Gaboriaud-Kolar
authors.forename: Bruno Ndjakou
authors.initials: BN
authors.lastname: Lenta
authors.forename: Jean Duplex
authors.initials: JD
authors.lastname: Wansi
authors.forename: Didier
authors.initials: D
authors.lastname: Buisson
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Mouray
authors.forename: Philippe
authors.initials: P
authors.lastname: Grellier
authors.forename: Philippe M
authors.initials: PM
authors.lastname: Loiseau
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Lallemand
authors.forename: Sylvie
authors.initials: S
authors.lastname: Michel
mesh_terms: D000981:Antiprotozoal Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001577:Benzophenones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D028084:Clusiaceae / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D007893:Leishmania donovani / Q000187:drug effects*; D015394:Molecular Structure; D021261:Parasitic Sensitivity Tests; D010963:Plasmodium falciparum / Q000187:drug effects*; D012639:Seeds / Q000737:chemistry; D013329:Structure-Activity Relationship; D014346:Trypanosoma brucei brucei / Q000187:drug effects*
chemical_list: D000981:Antiprotozoal Agents; D001577:Benzophenones; C558133:guttiferone A
keywords: Antiparasitic activities; Guttiferone A derivatives; Natural products; Semi-synthesis; Substitution on the catechol ring