New potential antimalarial agents: Synthesis and biological activities of original diaza-analogs of phenanthrene

Several diaza-analogs of phenanthrene derived from 3-amino, 5-amino, 6-amin o, 8-aminoquinolines, and 5-aminoisoquinoline were prepared to evaluate the ir antiplasmodial activities. All compounds showed mild to good activity in vitro, both on a Nigerian chloroquino-sensitive strain and on the chloroqu ino-resistant FcB1-Columbia and FcM29 strains. The position of the intracyc lic nitrogen atom is shown to be crucial for the activities (best results a re obtained with a 1,10-phenanthroline skeleton). In regard to the particul ar properties of this structure (metalloprotease inhibition activity by che lating divalent metal ions), the potential chelating site of the molecule w as blocked, In this case, the biological activity of the compound was great ly enhanced, showing that the mechanism of action of such a compound is pro bably not correlated to metalloprotease inhibition activity.