glaucarubin and chaparrinone

Hannoa chlorantha and Hannoa klaineana (Simaroubaceae) are used in traditional medicine of Central African countries against fevers and malaria. Four stem bark extracts from H. klaineana and four quassinoids from H. chlorantha were examined in vitro against Plasmodium falciparum NF 54. The extracts displayed good activities, while the quassinoids were highly active, with IC50 values well below 1 microgram ml-1, those of chaparrinone and 15-desacetylundulatone being much lower than 0.1 microgram ml-1 (0.037 and 0.047 microgram ml-1, respectively). Chaparrinone is five times more active than 14-hydroxychaparrinone against P. falciparum, indicating that the hydroxyl function at C-14 is unfavourable for antiplasmodial activity. As 14-hydroxychaparrinone has a seven-times higher cytotoxic activity against P-388 cells than chaparrinone, the latter compound has the better antiplasmodial therapeutic index. All four quassinoids were evaluated in vivo in a standard 4-day test as well. 15-Desacetylundulatone was proven to be the most active compound, almost totally suppressing the parasitaemias of OF1 mice for at least 7 days, while both chaparrinone and 14-hydroxychaparrinone were active for 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 effects. The keto function at C-2 in 15-desacetylundulatone is apparently of crucial importance for its high activity. 6-alpha-Tigloyloxyglaucarubol was not active at all. Chaparrinone is considered the most interesting of the investigated quassinoids and its in-vivo antimalarial potential will be examined further.

Topics: Animals; Antimalarials; Cell Survival; Female; Glaucarubin; Leukemia P388; Malaria; Mice; Plant Extracts; Plant Roots; Plants, Medicinal; Plasmodium berghei; Plasmodium falciparum; Quassins; Seeds; Structure-Activity Relationship; Tumor Cells, Cultured

Several quassinoids, obtained by isolation and derivatization from Simaba multiflora and Soulamea soulameoides, were evaluated for growth inhibitory and insecticidal effects against the tobacco budworm (Heliothis virescens) and for antifeedant effects against H. virescens and the fall armyworm (Spodoptera frugiperda). The relative activity of the quassinoids as insect growth inhibitors generally paralleled their known relative potency as antileukemic and cytotoxic agents.

Topics: Animals; Antineoplastic Agents, Phytogenic; Chemical Phenomena; Chemistry; Diterpenes; Eating; Glaucarubin; Insecta; Insecticides; Larva; Phenanthrenes; Quassins

The growth of Plasmodium falciparum in vitro was markedly inhibited by certain quassinoids (the bitter principles from plants of the family Simaroubaceae). The most active compound, simalikalactone D, gave complete inhibition at 0.005 microgram/ml. Glaucarubinone an soularubinone were equally effective at 0.006 microgram/ml, whereas chaparrinone and simarolide had little effect even at 0.01 microgram/ml. These relative activities are parallel to the antineoplastic activities of these materials.

Topics: Chloroquine; Dose-Response Relationship, Drug; Drug Resistance, Microbial; Glaucarubin; Phenanthrenes; Plasmodium falciparum; Quassins

Topics: Avian Sarcoma Viruses; Cell Transformation, Viral; DNA; DNA Replication; Dose-Response Relationship, Drug; Glaucarubin; Lactones; Leucine; Phenanthrenes; Protein Biosynthesis; Quassins; RNA; Structure-Activity Relationship