Potential anticancer activity of naturally occurring and semisynthetic derivatives of aculeatins A and B from Amomum aculeatum.
Activity-guided fractionation of hexanes- and CHCl 3-soluble extracts of Amomum aculeatum leaves, collected in Indonesia, led to the isolation of three new dioxadispiroketal-type ( 3- 5) and two new oxaspiroketal-type ( 6 and 7) derivatives. Nine semisynthetic derivatives ( 1a- 1h and 2a) of the parent compounds, aculeatins A ( 1) and B ( 2), were prepared. All isolates and semisynthetic compounds were tested against a small panel of human cell lines. Of these, aculeatin A ( 1; ED 50 0.2-1.0 microM) was found to be among the most cytotoxic of the compounds tested and was further evaluated in an in vivo hollow fiber assay; it was found to be active against MCF-7 (human breast cancer) cells implanted intraperitoneally at doses of 6.25, 12.5, 25, and 50 mg/kg. However, when 1 was tested using P388 lymphocytic leukemia and human A2780 ovarian carcinoma in vivo models, it was deemed to be inactive at the doses used.
Chin
Young-Won
YW
Division of Medicinal Chemsitry and Pharmacognosy, The Ohio State University, Columbus, Ohio 43210, USA.
Salim
Angela A
AA
Su
Bao-Ning
BN
Mi
Qiuwen
Q
Chai
Hee-Byung
HB
Riswan
Soedarsono
S
Kardono
Leonardus B S
LB
Ruskandi
Agus
A
Farnsworth
Norman R
NR
Swanson
Steven M
SM
Kinghorn
A Douglas
AD
D000473:Alkanes / Q000138:chemical synthesis / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D035801:Amomum / Q000737:chemistry*; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000138:chemical synthesis / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D003512:Cyclohexanones; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006801:Humans; D007941:Leukemia P388; D010946:Plants, Medicinal / Q000737:chemistry*; D013141:Spiro Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology
D000473:Alkanes; D000972:Antineoplastic Agents, Phytogenic; D003512:Cyclohexanones; D013141:Spiro Compounds; C476177:aculeatin A; C476176:aculeatin B