Cytotoxic constituents from the stem bark of Dichapetalum gelonioides collected in the Philippines.
Fractionation of an ethyl acetate-soluble extract of the stem bark of Dichapetalum gelonioides, collected in the Philippines, using the LNCaP (hormone-dependent human prostate) cell line as a monitor, led to the purification of three dichapetalin-type triterpenoids [dichapetalins A (1), I (2), and J (3)], along with two dolabrane norditerpenoids (6, 7), and the additional triterpenoids zeylanol (8), 28-hydroxyzeylanol (9), and betulinic acid. Since compounds 1-3 exhibited promising selectivity against the SW626 (human ovarian cancer) cell line, a re-collection of the plant material was carried out, to obtain more of these compounds for additional biological testing. Two further phenylpyranotriterpenoids [dichapetalins K (4) and L (5)] were isolated from the re-collected plant material. The structures of the new compounds 2-5 and 9 were determined on the basis of spectroscopic data interpretation, and the relative configuration of 6 was confirmed using X-ray crystallography. Compounds 4-6 and the methyl ester, 6a, exhibited broad cytotoxic activity when tested against a panel of human tumor cell lines. Dichapetalin A (1) was not active when evaluated in an in vivo hollow fiber assay in the dose range 1-6 mg/kg.
Program for Collaborative Research in the Pharmaceutical Sciences, and the Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois at Chicago, 60612, USA.
Liqiong
L
Fang
Aiko
A
Ito
Hee-Byung
HB
Chai
Qiuwen
Q
Mi
William P
WP
Jones
Domingo R
DR
Madulid
Mildred B
MB
Oliveros
Qi
Q
Gao
Jimmy
J
Orjala
Norman R
NR
Farnsworth
Djaja D
DD
Soejarto
Geoffrey A
GA
Cordell
Steven M
SM
Swanson
John M
JM
Pezzuto
A Douglas
AD
Kinghorn
D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D004224:Diterpenes / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D029581:Malpighiaceae / Q000737:chemistry*; D015394:Molecular Structure; D053978:Pentacyclic Triterpenes; D010679:Philippines; D024301:Plant Bark / Q000737:chemistry; D010946:Plants, Medicinal / Q000737:chemistry*; D014315:Triterpenes / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D000094062:Betulinic Acid
D000972:Antineoplastic Agents, Phytogenic; D004224:Diterpenes; D053978:Pentacyclic Triterpenes; D014315:Triterpenes; D000094062:Betulinic Acid