Synthesis and antimalarial activity of new haemanthamine-type derivatives.
Thirty one derivatives were prepared from the natural alkaloids haemanthamine (1), haemanthidine (2) and 11-hydroxyvittatine (3). They were evaluated for their in vitro antimalarial activity against chloroquine-sensitive strains of Plasmodium falciparum and some structure-activity relationships were outlined. For haemanthamine derivatives having a methoxy group at C-3, the presence of a free hydroxyl group at C-11 is important for the activity. The double bond at C-1-C-2 plays also an important role to achieve good inhibitory activity. Compound 35 with two nicotinate groups at C-3 and at C-11 was the most active compound with a IC(50) = 0.8 ± 0.06 μM.
Instituto Universitario de Bio-Orgánica Antonio González, Av. Astrofísico Francisco Sánchez 2, 38206, Departamento de Química Orgánica, Universidad de La Laguna, Tenerife, Spain.
Juan C
JC
Cedrón
David
D
Gutiérrez
Ninoska
N
Flores
Ángel G
ÁG
Ravelo
Ana
A
Estévez-Braun
D047151:Amaryllidaceae Alkaloids / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D000962:Antimalarials / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D008968:Molecular Conformation; D021261:Parasitic Sensitivity Tests; D010617:Phenanthridines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D010963:Plasmodium falciparum / Q000187:drug effects*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D047151:Amaryllidaceae Alkaloids; D000962:Antimalarials; D010617:Phenanthridines; C462104:hemanthamine