Rearranged diterpenoids from the biotransformation of ent-trachyloban-18-oic acid by Rhizopus arrhizus.
In our search for inhibitors of the antiapoptotic protein Bcl-xL, investigation of Xylopia caudata afforded a new diterpenoid, ent-trachyloban-4beta-ol (2), and five known ent-trachylobane or ent-atisane compounds. Only ent-trachyloban-18-oic acid (1) exhibited weak binding activity to Bcl-xL. These compounds exhibited cytotoxicity against KB and HCT-116 cell lines with IC(50) values between 10 and 30 microM. Bioconversion of compound 1 by Rhizopus arrhizus afforded new hydroxylated metabolites (3-7) of the ent-trachylobane and ent-kaurene type and compound 8, with a rearranged pentacyclic carbon framework that was named rhizopene. Compounds 3-8 were noncytotoxic to the two cancer cell lines, and compounds 3 and 5 exhibited only weak binding affinity for Bcl-xL.
Leverrier
Aurélie
A
Centre de Recherche de Gif, Institut de Chimie des Substances Naturelles, CNRS, 1 Avenue de la Terrasse, 91198 Gif-sur-Yvette Cedex, France.
Martin
Marie-Thérèse
MT
Servy
Claudine
C
Ouazzani
Jamal
J
Retailleau
Pascal
P
Awang
Khalijah
K
Mukhtar
Mat Ropi
MR
Guéritte
Françoise
F
Litaudon
Marc
M
D001711:Biotransformation; D004224:Diterpenes / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D045325:HCT116 Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D007624:KB Cells; D008296:Malaysia; D015394:Molecular Structure; D024301:Plant Bark / Q000737:chemistry; D012233:Rhizopus / Q000378:metabolism*; D054336:Xylopia / Q000737:chemistry*; D051020:bcl-X Protein / Q000187:drug effects*
D004224:Diterpenes; D051020:bcl-X Protein; C550948:ent-trachyloban-18-oic acid; C550947:ent-trachyloban-4beta-ol