Cholic acid derivatives as 1,2,4,5-tetraoxane carriers: Structure and antimalarial and antiproliferative activity
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2000
Authors
Opsenica, Dejan
Pocsfalvi, G.
Juranić, Zorica

Tinant, Bernard
Declercq, J.-P.
Kyle, D.E.
Milhous, Wilbur K.
Šolaja, Bogdan

Article (Published version)

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Cholic acid-derived 1,2,4,5-tetraoxanes were synthesized in order to explore the influence of steroid carrier on its antimalarial and antiproliferative activity in vitro. Starting with chiral ketones, cis and trans series of diastereomeric tetraoxanes were obtained, and the cis series was found to be ~2 times as active as the trans against Plasmodium falciparum D6 and W2 clones. The same tendency was observed against human melanoma (Fem-X) and human cervix carcinoma (HeLa) cell lines. The amide C(24) termini, for the first time introduced into the carrier molecule of a tetraoxane pharmacophore, significantly enhanced both antimalarial and antiproliferative activity, as compared to the corresponding methyl esters, with cis-bis(N-propylamide) being most efficient against the chloroquine-susceptible D6 clone (IC50 = 9.29 nM). cis- and trans-bis(N-propylamides) were also screened against PBMC, and PHA-stimulated PBMC, showing a cytotoxicity/antimalarial potency ratio of 1/10 000.
Source:
Journal of Medicinal Chemistry, 2000, 43, 17, 3274-3282Publisher:
- Amer Chemical Soc, Washington
DOI: 10.1021/jm000952f
ISSN: 0022-2623
PubMed: 10966746