Leishmanicidal, antiplasmodial and cytotoxic activity of indole alkaloids from Corynanthe pachyceras.
Five indole alkaloids, corynantheidine, corynantheine, dihydrocorynantheine, alpha-yohimbine and corynanthine were isolated from bark of Corynanthe pachyceras K. Schum. (Rubiaceae). The structures were established by spectroscopic methods, including previously unreported assignment of all 1H-NMR resonances by COSY and NOESY experiments. These and related alkaloids showed pronounced activity against Leishmania major promastigotes (IC50 at the micromolar level) but no significant in vitro antiplasmodial activity (against chloroquine-sensitive Plasmodium falciparum). Cytotoxicity assessed with drug sensitive KB-3-1 and multidrug-resistant KB-V1 cell lines was low; the alkaloids are apparently not substrates for the P-glycoprotein (P-170) efflux pump.
Staerk
D
D
Department of Medicinal Chemistry, Royal Danish School of Pharmacy, Copenhagen, Denmark.
Lemmich
E
E
Christensen
J
J
Kharazmi
A
A
Olsen
C E
CE
Jaroszewski
J W
JW
D000470:Alkaloids / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D000981:Antiprotozoal Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D006801:Humans; D007211:Indoles / Q000737:chemistry*; D018320:Leishmania major / Q000187:drug effects; D010946:Plants, Medicinal / Q000737:chemistry*; D010963:Plasmodium falciparum / Q000187:drug effects; D014407:Tumor Cells, Cultured
D000470:Alkaloids; D000972:Antineoplastic Agents, Phytogenic; D000981:Antiprotozoal Agents; D007211:Indoles