ANTIMALARIAL AND CYTOTOXIC POTENTIAL OF 4 QUASSINOIDS FROM HANNOA-CHLORANTHA AND HANNOA-KLAINEANA, AND THEIR STRUCTURE-ACTIVITY-RELATIONSHIPS

Hannoa chlorantha and Hannoa klaineana (Simaroubaceae) are used in tra ditional medicine of Central African countries against fevers and mala ria. Four stem bark extracts from H. klaineana and four quassinoids fr om H. chlorantha were examined in vitro against Plasmodium falciparum NF 54. The extracts displayed good activities, while the quassinoids w ere highly active, with IC50 values well below 1 mu g ml(-1), those of chaparrinone and 15-desacetylundulatone being much lower than 0.1 mu g ml(-1) (0.037 and 0.047 mu g ml(-1), respectively). Chaparrinone is five times more active than 14-hydroxychaparrinone against P. falcipar um, indicating that the hydroxyl function at C-14 is unfavourable for antiplasmodial activity. As 14-hydroxychaparrinone has a seven-times h igher cytotoxic activity against P-388 cells than chaparrinone, the la tter compound has the better antiplasmodial therapeutic index. All fou r quassinoids were evaluated in vivo in a standard 4-day test as well, 15-Desacetylundulatone was proven to be the most active compound, alm ost totally suppressing the parasitaemias of OF1 mice for at least 7 d ays, while both chaparrinone and 14-hydroxychaparrinone were active fo r at least 4 days. Quassinoids have ED50 values much lower than 50 mg kg(-1) body weight day(-1) and none of them caused obvious side effect s. The keto function at C-2 in 15-desacetylundulatone is apparently of crucial importance for its high activity. 6-alpha-Tigloyloxyglaucarub ol was not active at all. Chaparrinone is considered the most interest ing of the investigated quassinoids and its in-vivo antimalarial poten tial will be examined further. (C) 1998 Australian Society for Parasit ology. Published by Elsevier Science Ltd.