title: New potential antimalarial agents: synthesis and biological activities of original diaza-analogs of phenanthrene.
abstract: Several diaza-analogs of phenanthrene derived from 3-amino, 5-amino, 6-amino, 8-aminoquinolines, and 5-aminoisoquinoline were prepared to evaluate their antiplasmodial activities. All compounds showed mild to good activitiy in vitro, both on a Nigerian chloroquino-sensitive strain and on the chloroquino-resistant FcB1-Columbia and FcM29 strains. The position of the intracyclic nitrogen atom is shown to be crucial for the activities (best results are obtained with a 1,10-phenanthroline skeleton). In regard to the particular properties of this structure (metalloprotease inhibition activitiy by chelating divalent metal ions), the potential chelating site of the molecule was blocked. In this case, the biological activity of the compound was greatly enhanced, showing that the mechanism of action of such a compound is probably not correlated to metalloprotease inhibition activity.
authors.affiliation: Laboratoire de Chimie Organique Pharmaceutique, Faculte de Pharmacie, Montpellier, France.
authors.forename: A D
authors.initials: AD
authors.lastname: Yapi
authors.forename: M
authors.initials: M
authors.lastname: Mustof
authors.forename: A
authors.initials: A
authors.lastname: Valentin
authors.forename: O
authors.initials: O
authors.lastname: Chavignon
authors.forename: J C
authors.initials: JC
authors.lastname: Teulade
authors.forename: M
authors.initials: M
authors.lastname: Mallie
authors.forename: J P
authors.initials: JP
authors.lastname: Chapat
authors.forename: Y
authors.initials: Y
authors.lastname: Blache
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002614:Chelating Agents / Q000737:chemistry; D004353:Drug Evaluation, Preclinical; D006367:HeLa Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D010616:Phenanthrenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D010618:Phenanthrolines / Q000737:chemistry; D010963:Plasmodium falciparum / Q000187:drug effects
chemical_list: D000962:Antimalarials; D002614:Chelating Agents; D010616:Phenanthrenes; D010618:Phenanthrolines; C025205:1,10-phenanthroline