title: Pharmacomodulations on new organometallic complexes of Ir, Pt, Rh, Pd, Os: in vitro and in vivo trypanocidal study against Trypanosoma brucei brucei.
abstract: New organometallic complexes have been synthesized by association of an active organic molecule with a metallic element such as Pt, Rh, Ir, Pd, Os. Their trypanocidal activity was studied in vitro and in vivo against T. b. brucei. The more active compounds were pentamidine derivatives. The Ir- COD-pentamidine complex, and Iridium (I) cationic and organometallic complex showed and in vitro activity at 60 micrograms/l. Moreover, all infected mice were cured by this compound subcutaneously administered in a single dose at 0.5 mg/kg (0.317 mumol/kg). In the same conditions, pentamidine cured all the mice at 5 mumol/kg. Ir-COD-pentamidine (or P1995) was 16 fold more efficient than pentamidine. Since the chemotherapeutic index of this molecule was 7.5 fold higher than those of pentamidine, P1995 can be considered as a potential trypanocidal drug of the future.
authors.affiliation: Biologie et Contrôle des Organismes Parasites, Université Paris-Sud, Châtenay-Malabry, France.
authors.forename: P M
authors.initials: PM
authors.lastname: Loiseau
authors.forename: D G
authors.initials: DG
authors.lastname: Craciunescu
authors.forename: J C
authors.initials: JC
authors.lastname: Doadrio-Villarejo
authors.forename: G
authors.initials: G
authors.lastname: Certad-Fombona
authors.forename: P
authors.initials: P
authors.lastname: Gayral
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D004361:Drug Tolerance; D005260:Female; D007495:Iridium / Q000494:pharmacology / Q000627:therapeutic use; D007854:Lead / Q000494:pharmacology / Q000627:therapeutic use; D051379:Mice; D009942:Organometallic Compounds / Q000494:pharmacology* / Q000627:therapeutic use; D009992:Osmium / Q000494:pharmacology / Q000627:therapeutic use; D010984:Platinum / Q000494:pharmacology / Q000627:therapeutic use; D013329:Structure-Activity Relationship; D014344:Trypanocidal Agents / Q000494:pharmacology* / Q000627:therapeutic use; D014346:Trypanosoma brucei brucei / Q000187:drug effects*; D014353:Trypanosomiasis, African / Q000188:drug therapy*
chemical_list: D009942:Organometallic Compounds; D014344:Trypanocidal Agents; D009992:Osmium; D007854:Lead; D007495:Iridium; D010984:Platinum