Antitrypanosomal naphthylisoquinoline alkaloids and related compounds.
In view of the need to develop new drugs against human African trypanosomiasis, a series of naturally occurring naphthylisoquinoline alkaloids, axially chiral acetogenic products derived from tropical plants, have been investigated for their activity against Trypanosoma brucei brucei TC 221. Likewise compounds corresponding to the two molecular portions, the naphthalene and the isoquinoline parts were tested, as well as molecules related to the central biaryl core of the alkaloids. Among all compounds tested, the natural, genuine alkaloids themselves, in particular dioncophylline B with its biaryl system and a moderate number of free hydroxy functions, showed the highest activities. Our results demonstrate that naphthylisoquinoline alkaloids constitute an interesting novel class of antitrypanosomal compounds worth further optimization.
Bringmann
G
G
Institut für Organische Chemie, Dept. of Tropical Medicine and Epidemic Control, Würzburg, Germany. bringmann@chmie.uni-wuerzburg.de
Hoerr
V
V
Holzgrabe
U
U
Stich
A
A
D000470:Alkaloids / Q000138:chemical synthesis* / Q000494:pharmacology*; D000818:Animals; D015195:Drug Design; D007202:Indicators and Reagents; D007546:Isoquinolines / Q000138:chemical synthesis* / Q000494:pharmacology*; D008970:Molecular Weight; D010946:Plants, Medicinal / Q000737:chemistry; D012997:Solvents; D013329:Structure-Activity Relationship; D014344:Trypanocidal Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D014346:Trypanosoma brucei brucei / Q000187:drug effects
D000470:Alkaloids; D007202:Indicators and Reagents; D007546:Isoquinolines; D012997:Solvents; D014344:Trypanocidal Agents