New antimalarials with a triterpenic scaffold from Momordica balsamina.
Bioassay-guided fractionation of the methanol extract of Momordica balsamina led to the isolation of three new cucurbitane-type triterpenoids, balsaminols C-E (1-3). Their structures were elucidated on the basis of spectroscopic methods including 2D NMR experiments (COSY, HMQC, HMBC and NOESY). Balsaminols C-E, together with ten cucurbitacins isolated from the same plant (4-13), were evaluated for their antimalarial activity against the Plasmodium falciparum chloroquine-sensitive strain 3D7 and the chloroquine-resistant clone Dd2. Most of the compounds displayed antimalarial activity. Compounds 9 and 12 revealed the highest antiplasmodial effects against both strains (IC50 values: 4.6, and 7.4 microM, 3D7, respectively; 4.0, and 8.2 microM, Dd2, respectively). Structure-activity relationships are discussed. Furthermore, the preliminary toxicity toward human cells of compounds 1-5 and 9 was investigated in breast cancer cell line (MCF-7). Compounds were inactive or showed weak toxicity (IC50 values>19.0).
Ramalhete
Cátia
C
iMed.UL, Faculty of Pharmacy, University of Lisbon, Av. das Forças Armadas, 1600-083 Lisbon, Portugal.
Lopes
Dinora
D
Mulhovo
Silva
S
Molnár
Joseph
J
Rosário
Virgílio E
VE
Ferreira
Maria-José U
MJ
D000962:Antimalarials / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy; D008958:Models, Molecular; D029775:Momordica / Q000737:chemistry*; D010963:Plasmodium falciparum / Q000187:drug effects*; D013329:Structure-Activity Relationship; D014315:Triterpenes / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*
D000962:Antimalarials; D014315:Triterpenes