10-, 12-, and 29-hydroxybullatacinones: new cytotoxic Annonaceous acetogenins from Annona bullata Rich (Annonaceae).
In our continuing activity-directed search for new antitumor compounds, using brine shrimp lethality (BST), mixtures of three additional pairs (1-6) of bis-THF ketolactone acetogenins were isolated from the ethanol extract of the bark of Annona bullata Rich. (Annonaceae). Compared with (2,4-cis and trans)-bullatacinone (7 and 8), these new compounds each have one more aliphatic OH group at a different position on the hydrocarbon chain, and, thus, were named (2,4-cis and trans)-10-hydroxybullatacinone (1 and 2), (2,4-cis and trans)-12-hydroxybullatacinone (3 and 4), and (2,4-cis and trans)-29-hydroxybullatacinone (5 and 6). These mixtures all showed potent activities in the brine shrimp lethality test (BST) and exhibited cytotoxicities comparable to those of adriamycin against human solid tumor cells in culture with selectivities exhibited especially toward the breast cancer cell line (MCF-7).
Gu
Z M
ZM
Department of Medicinal Chemistry and Pharmacognosy, School of Pharmacy and Pharmacal Sciences, Purdue University, West Lafayette, Indiana 47907.
Fang
X P
XP
Hui
Y H
YH
McLaughlin
J L
JL
D000107:Acetylation; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000302:isolation & purification* / Q000633:toxicity*; D001156:Artemia; D005663:Furans / Q000302:isolation & purification* / Q000633:toxicity; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008968:Molecular Conformation; D010936:Plant Extracts / Q000737:chemistry / Q000302:isolation & purification* / Q000633:toxicity*; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000972:Antineoplastic Agents, Phytogenic; D005663:Furans; D010936:Plant Extracts; C061021:bullatacinone