title: Synthesis and antiprotozoal activity of original porphyrin precursors and derivatives.
abstract: Importance of heme in African trypanosomes, Leishmania sp. and Plasmodium sp. metabolisms justifies considering the potential of porphyrins and their precursors and derivatives as potential antiparasitic agents by interfering with heme metabolism. Consequently, twenty-four porphyrin precursors and derivatives were evaluated against Leishmania donovani, Trypanosoma brucei and Plasmodium sp. The best active compound against Trypanosoma brucei brucei was a new porphyrin derivative; compound 4i, with a MEC value of 6.25 μM justifying further in vivo evaluation. Whereas these compounds were not active against intramacrophage amastigotes of L. donovani, another new porphyrin derivative, compound 4f was active in vitro against Plasmodium falciparum at 20 nM and a slight delay of mice survival was observed on the Plasmodium berghei/Swiss mice model at 50 μmol/kg/day × 4. Pharmacomodulations should be further developed relying on a better knowledge on the porphyrin behaviour into the parasites comparatively to host cells.
authors.affiliation: UMR CNRS 8076, LERMIT, Université Paris-Sud, Laboratoire de Pharmacognosie, UFR de Pharmacie, Châtenay-Malabry F-92296, France.
authors.forename: Zahra
authors.initials: Z
authors.lastname: Abada
authors.forename: Sandrine
authors.initials: S
authors.lastname: Cojean
authors.forename: Sébastien
authors.initials: S
authors.lastname: Pomel
authors.forename: Laurent
authors.initials: L
authors.lastname: Ferrié
authors.forename: Bernardin
authors.initials: B
authors.lastname: Akagah
authors.forename: Anh Tuan
authors.initials: AT
authors.lastname: Lormier
authors.forename: Philippe M
authors.initials: PM
authors.lastname: Loiseau
authors.forename: Bruno
authors.initials: B
authors.lastname: Figadère
mesh_terms: D000981:Antiprotozoal Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D007893:Leishmania donovani / Q000187:drug effects*; D015394:Molecular Structure; D021261:Parasitic Sensitivity Tests; D010961:Plasmodium / Q000187:drug effects*; D011166:Porphyrins / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014346:Trypanosoma brucei brucei / Q000187:drug effects*
chemical_list: D000981:Antiprotozoal Agents; D011166:Porphyrins
keywords: Anti-malaric; Leishmanicid; Metal complexes; Trypanocid