title: Antitrypanosomal activities of acetylated bruceines A and C; a structure-activity relationship study.
abstract: The crude extract of Brucea javanica showed strong in vitro inhibitory activity against Trypanosoma evansi. Among the isolated quassinoids, bruceines A, C, and bruceantinol were found to be the most potent compounds against T. evansi. To gain a deeper understanding of the relationship between the free hydroxyl groups and the activity, several O-acetylated derivatives of bruceines A and C were synthesized and their in vitro antitrypanosomal activities against trypomastigotes of T. evansi were examined and compared with those of the original compounds. The following structure-activity relationships were observed: (1) the free hydroxyl groups at positions C-3, C-11, and C-12 are essential for antitrypanosomal activity; (2) the C-11 and C-12 hydroxyl groups are more important for the activity than the enolic hydroxyl group at C-3, and; (3) the free hydroxyl group at C-4' of bruceine C does not have any significant effect on the activity.
authors.affiliation: Laboratory of Parasitology, Department of Disease Control, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo 060-0818, Japan.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Elkhateeb
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Tosa
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Matsuura
authors.forename: Kensuke
authors.initials: K
authors.lastname: Nabeta
authors.forename: Ken
authors.initials: K
authors.lastname: Katakura
mesh_terms: D000107:Acetylation; D032269:Brucea / Q000737:chemistry; D005638:Fruit; D015394:Molecular Structure; D036702:Quassins / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014344:Trypanocidal Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D014345:Trypanosoma / Q000187:drug effects*
chemical_list: D036702:Quassins; D014344:Trypanocidal Agents; C571070:bruceine C; C024964:bruceine A