jm0509492_si_001.pdf (22.49 MB)
Miliusanes, A Class of Cytotoxic Agents from Miliusa sinensis
journal contribution
posted on 2006-01-26, 00:00 authored by Hong-Jie Zhang, Cuiying Ma, Nguyen Van Hung, Nguyen Manh Cuong, Ghee Teng Tan, Bernard D. Santarsiero, Andrew D. Mesecar, D. Doel Soejarto, John M. Pezzuto, Harry H. S. FongBioassay-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.