Cytotoxic pentacyclic triterpenoids from Combretum sundaicum and Lantana camara as inhibitors of Bcl-xL/BakBH3 domain peptide interaction.
In an effort to discover potent inhibitors of the antiapoptotic protein Bcl-xL, a systematic in vitro evaluation was undertaken on extracts prepared from various parts of Vietnamese plants. The ethyl acetate extracts obtained from the leaves and flowers of Combretum sundaicum and the leaves of Lantana camara were selected for their interaction with the Bcl-xL/Bak association. Bioassay-guided purification of these species led to the isolation of 15 pentacyclic triterpenoids (1-15) possessing olean-12-en-28-oic acid and olean-12-en-29-oic acid aglycons, of which compounds 1-6 and 8-10 are new. Five compounds exhibited binding activity with K(i) values between 5.3 and 17.8 microM. The cytotoxic activity of 1-15 was also evaluated on various cancer cell lines.
Litaudon
Marc
M
Institut de Chimie des Substances Naturelles, UPR2301, CNRS, 91198 Gif-sur-Yvette, France. litaudon@icsn.cnrs-gif.fr
Jolly
Claire
C
Le Callonec
Catherine
C
Cuong
Dao Din
DD
Retailleau
Pascal
P
Nosjean
Olivier
O
Nguyen
Van Hung
VH
Pfeiffer
Bruno
B
Boutin
Jean A
JA
Guéritte
Françoise
F
D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D029765:Combretum / Q000737:chemistry*; D004354:Drug Screening Assays, Antitumor; D035264:Flowers / Q000737:chemistry; D006801:Humans; D032410:Lantana / Q000737:chemistry*; D015394:Molecular Structure; D018515:Plant Leaves / Q000187:drug effects; D010946:Plants, Medicinal / Q000737:chemistry*; D014315:Triterpenes / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D014744:Vietnam; D050998:bcl-2 Homologous Antagonist-Killer Protein / Q000187:drug effects*; D051020:bcl-X Protein / Q000187:drug effects*
D000972:Antineoplastic Agents, Phytogenic; D014315:Triterpenes; D050998:bcl-2 Homologous Antagonist-Killer Protein; D051020:bcl-X Protein