Antiplasmodial triterpenoids from Ekebergia capensis.
From the stem bark of Ekebergia capensis, 10 new triterpenoid compounds, ekeberins A (1), B (2), C1 (3), C2 (4), C3 (5), D1 (6), D2 (7), D3 (8), D4 (9), and D5 (10), were isolated together with 17 known compounds. The structures of these new compounds were elucidated on the basis of the results of spectroscopic analysis, and the absolute configuration of compounds 6-10 were determined by partial synthesis from known compounds and using the Mosher ester method. Several of these compounds were screened in vitro against both chloroquine (CQ)-sensitive and -resistant Plasmodium falciparum isolates and were found to exhibit moderate antiplasmodial activity, with compounds 20 (7-deacetoxy-7-oxogedunin) and 27 (2-hydroxymethyl-2,3,22,23-tetrahydroxy-2,6,10,15,19,23-hexamethyl-6,10,14,18-tetracosatetraene) showing IC50 values of 6 and 7 microM, respectively. Compound 27 at a dose of 500 mg/kg showed moderate parasitemia suppression of 52.9% against P. berghei NK 65 in a mouse model.
Murata
Toshihiro
T
School of Pharmaceutical Sciences, University of Shizuoka, 52-1, Yada, Suruga-ku, Shizuoka 422-8526, Japan.
Miyase
Toshio
T
Muregi
Francis Wamakima
FW
Naoshima-Ishibashi
Yasuko
Y
Umehara
Kaoru
K
Warashina
Tsutomu
T
Kanou
Shigeyuki
S
Mkoji
Gerald M
GM
Terada
Mamoru
M
Ishih
Akira
A
D000818:Animals; D000962:Antimalarials / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D002738:Chloroquine / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D007630:Kenya; D029582:Meliaceae / Q000737:chemistry*; D051379:Mice; D015394:Molecular Structure; D021261:Parasitic Sensitivity Tests; D024301:Plant Bark / Q000737:chemistry; D018547:Plant Stems / Q000737:chemistry; D010946:Plants, Medicinal / Q000737:chemistry*; D010962:Plasmodium berghei / Q000187:drug effects; D010963:Plasmodium falciparum / Q000187:drug effects; D014315:Triterpenes / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*
D000962:Antimalarials; D014315:Triterpenes; D002738:Chloroquine