TY - JOUR
T1 - Miliusanes, a class of cytotoxic agents from Miliusa sinensis
AU - ZHANG, Hongjie
AU - Ma, Cuiying
AU - Van Hung, Nguyen
AU - Cuong, Nguyen Manh
AU - Tan, Ghee Teng
AU - Santarsiero, Bernard D.
AU - Mesecar, Andrew D.
AU - Soejarto, D. Doel
AU - Pezzuto, John M.
AU - Fong, Harry H.S.
N1 - All work involving plant sample collection, taxonomic identification, bioassay-guided chemical isolation, and structure elucidation in connection with this paper was carried out under a grant administered by the Fogarty International Center, NIH (Grant 1 UO1-TW01015-01), as part of an ICBG program, through funds from NIH, NSF, and USDAFAS. Permission for the collection and export of plant material for this study was granted by the Ministry of Agriculture and Rural Development (Hanoi, Vietnam) through a letter dated September 15, 1998, Ref. No. 3551/BNN/KHCN, and from the Cuc Phuong National Park, through a letter dated September 16, 1998.
PY - 2006/1/26
Y1 - 2006/1/26
N2 - Bioassay-directed fractionation of the leaves, twigs, and flowers of Miliusa sinensis Finet and Gagnep. (Annonaceae) led to the isolation of a new class of potential anticancer lead molecules. They are a cluster of compounds composed of a C18 carbon skeleton, a known but heretofore unnamed type, which we have designated as miliusane. Two known (1 and 2) as well as 20 new miliusanes (3-22) have been isolated and identified. They belong to two substructural classes of miliusanes. One subclass (1-19) was determined to be composed of a γ-lactone spiro-ring system, the opening of which led to the second group of compounds (21 and 22) containing a tetrahydrofuran ring system. Compounds 1-3, 5, 8, 9, 18, 20, and 21 demonstrated significant cytotoxic activity in our cancer cell line panel comprising KB, Col-2, LNCaP, Lu-1, MCF-7, and HUVEC. The structures were determined by spectroscopic and chemical methods. The structure of miliusate was further confirmed by X-ray crystallographic analysis. The absolute stereochemistry of miliusanes was established by the Mosher ester method. Forty-two modified miliusane derivatives were also prepared and evaluated for their cytotoxic activities.
AB - Bioassay-directed fractionation of the leaves, twigs, and flowers of Miliusa sinensis Finet and Gagnep. (Annonaceae) led to the isolation of a new class of potential anticancer lead molecules. They are a cluster of compounds composed of a C18 carbon skeleton, a known but heretofore unnamed type, which we have designated as miliusane. Two known (1 and 2) as well as 20 new miliusanes (3-22) have been isolated and identified. They belong to two substructural classes of miliusanes. One subclass (1-19) was determined to be composed of a γ-lactone spiro-ring system, the opening of which led to the second group of compounds (21 and 22) containing a tetrahydrofuran ring system. Compounds 1-3, 5, 8, 9, 18, 20, and 21 demonstrated significant cytotoxic activity in our cancer cell line panel comprising KB, Col-2, LNCaP, Lu-1, MCF-7, and HUVEC. The structures were determined by spectroscopic and chemical methods. The structure of miliusate was further confirmed by X-ray crystallographic analysis. The absolute stereochemistry of miliusanes was established by the Mosher ester method. Forty-two modified miliusane derivatives were also prepared and evaluated for their cytotoxic activities.
UR - http://www.scopus.com/inward/record.url?scp=31544443011&partnerID=8YFLogxK
U2 - 10.1021/jm0509492
DO - 10.1021/jm0509492
M3 - Journal article
C2 - 16420055
AN - SCOPUS:31544443011
SN - 0022-2623
VL - 49
SP - 693
EP - 708
JO - Journal of Medicinal Chemistry
JF - Journal of Medicinal Chemistry
IS - 2
ER -
