glaucarubin and Malaria

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

Cedronin was isolated from Simaba cedron Planchon (Simaroubaceae), a species popularly believed in South America to have antimalarial properties. It was examined for in vitro and in vivo antimalarial activities and for cytotoxicity against KB cells. Experimental results showed that cedronin was active against chloroquine-sensitive and resistant strain, with an IC50 of 0.25 micrograms/ml (0.65 mumol/ml). It was also found to be active in vivo against Plasmodium vinkei with an IC50 of 1.8 mg/kg (4.7 nM/kg) in the classic 4-day test. Cedronin belongs to the small group of quassinoids with a C19 basic skeleton and shows a rather low cytotoxicity against KB cells (IC50 = 4 micrograms/ml, 10.4 microM) as compared with C20 biologically active quassinoids; however its toxic/therapeutic ratio (10/1.8) remains lower than chloroquine (10/0.5).

Topics: Animals; Antimalarials; Chloroquine; Drug Resistance; Glaucarubin; Humans; In Vitro Techniques; KB Cells; Malaria; Male; Mice; Plant Extracts; Plasmodium; Plasmodium falciparum; Quassins

Prevention and treatment of malaria are endangered by the appearance of chemoresistance against the common anti-malarial drugs by Plasmodium falciparum. Today, only a quinoline derivative, mefloquine, is a safe and effective agent against P. falciparum. An in vitro antiplasmodial activity having been found for the quassinoid glaucarubinone we tested its in vivo therapeutic action on mice infected with a P. berghei strain. At low doses, glaucarubinone retarded mortality by exerting a partial, temporary, inhibition of parasitaemia; its toxicity, however, precludes, further applications at the present time.

Topics: Administration, Oral; Animals; Drug Evaluation, Preclinical; Female; Glaucarubin; Injections, Intraperitoneal; Malaria; Mice; Phenanthrenes; Plasmodium berghei

Fourteen quassinoids, obtained from simaroubaceous plants, were tested for in vitro antimalarial activity. All of these inhibited the incorporation of [3H]hypoxanthine into Plasmodium falciparum in vitro at concentrations below 0.41 microgram ml-1. The two most potent quassinoids, bruceantin and simalikalactone D, showed 50% inhibitory concentration values of 0.0008 and 0.0009 microgram ml-1, respectively. The results are compared with the antiamoebic, antileukemic, and cytotoxic activities of these compounds reported in the literature.

Topics: Amebicides; Animals; Antimalarials; Cell Survival; Erythrocytes; Glaucarubin; Humans; In Vitro Techniques; Leukemia P388; Malaria; Phenanthrenes; Plant Extracts; Plants, Medicinal; Plasmodium falciparum