strychnine and Malaria--Falciparum

Topics: Adolescent; Adult; Animals; Antimalarials; Child; Chloroquine; Double-Blind Method; Drug Resistance; Humans; Indole Alkaloids; Madagascar; Malaria, Falciparum; Middle Aged; Phytotherapy; Plasmodium falciparum; Strychnos; Young Adult

From the stem bark of Strychnos malacoclados, one new bisindole alkaloid, 3-hydroxylongicaudatine Y (1), was isolated along with the known alkaloids vomicine (2), bisnordihydrotoxiferine (3), divarine (4), longicaudatine (5), longicaudatine Y (6), and longicaudatine F (7). All the compounds were tested for their antimalarial activity against the chloroquine-sensitive 3D7 and -resistant W2 strains of Plasmodium falciparum. Longicaudatine was the most active compound with IC₅₀ values of 0.682 and 0.573 µM, respectively. The activity of compounds 1, 3, 4, 6, and 7 against the two strains ranged from 1.191 to 6.220 µM and 0.573 to 21.848 µM, respectively. Vomicine (2), the only monomer isolated, was inactive. The alkaloids of the longicaudatine-type ( 1, 5-7) were more active than those of the caracurine-type (3- 4). The presence of the ether bridge in the molecule seems to increase the antiplasmodial activity. Compounds 1, 5, and 7 were tested against the WI-38 human fibroblast cell line. Longicaudatine was the most cytotoxic compound with an IC₅₀ of 2.721 µM. Longicaudatine F was 40-46 times more active against the two strains of P. falciparum than against the human fibroblasts and was thus considered as the more selective alkaloid. The structures of the compounds were determined based on the analysis of their spectral data.

Topics: Alkaloids; Antiprotozoal Agents; Cameroon; Cell Line; Fibroblasts; Humans; Malaria, Falciparum; Phytotherapy; Plant Bark; Plant Extracts; Plant Stems; Plasmodium falciparum; Strychnos

Isostrychnopentamine (ISP) is an asymmetric indolomonoterpenic alkaloid isolated from the leaves of Strychnos usambarensis. The in vitro antiplasmodial activities against five Plasmodium falciparum cell lines were evaluated: ISP possessed an in vitro IC (50) near 0.1 microM against all P. falciparum cell lines tested (chloroquine-resistant and chloroquine-sensitive lines) and showed antiplasmodial selectivity compared to cytotoxicity on human cell lines. The stage-dependent susceptibility to a short exposure of ISP was then investigated. The ring stage was shown to be the most sensitive one, but all stages were affected by ISP treatment. By means of fluorescence microscopy, it was shown that ISP was not accumulated inside the food vacuole of the parasite. Finally, the in vivo antimalarial activities against the P. berghei NK173 and P. vinckei petteri murine strains were determined. The ED (50) in vivo was about 30 mg/kg/day by the intraperitoneal route (after 4 days treatment).

Topics: Alkaloids; Animals; Antimalarials; Carbolines; Cell Line, Tumor; Drug Resistance; Female; Humans; Malaria, Falciparum; Mice; Parasitic Sensitivity Tests; Phytotherapy; Plant Extracts; Plasmodium falciparum; Strychnos; Terpenes