9-Anilinoacridines as potential antileishmanial agents.
A number of 1'-substituted 9-anilinoacridines were evaluated for their activities against promastigote and amastigote forms of Leishmania major and for their toxicities to human Jurkat leukemia cells. Several compounds possessing 1'-NH-alkyl substituents produced more than 80% growth inhibition of macrophage-infected L. major amastigotes at or below a concentration of 1 microM. 1'-Hexylamino-9-anilinoacridine (compound 14) was the least toxic compound to human Jurkat cells, while it retained strong antileishmanial activity. There was a general trend for the more lipophilic compounds to show the greatest antileishmanial activity, whereas 3,6-di-NH2 substitution of the acridine nucleus reduced or eliminated activity. Some structure-activity relationships of the various compounds are discussed.
Mauël
J
J
Institute of Biochemistry, University of Lausanne, Epalinges, Switzerland.
Denny
W
W
Gamage
S
S
Ransijn
A
A
Wojcik
S
S
Figgitt
D
D
Ralph
R
R
D000677:Amsacrine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000981:Antiprotozoal Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002460:Cell Line; D006801:Humans; D007895:Leishmania tropica / Q000187:drug effects*; D016773:Leishmaniasis, Cutaneous / Q000188:drug therapy / Q000469:parasitology; D008264:Macrophages / Q000187:drug effects / Q000469:parasitology; D051379:Mice; D008811:Mice, Inbred DBA; D014407:Tumor Cells, Cultured
D000981:Antiprotozoal Agents; D000677:Amsacrine; C022202:9-anilinoacridine