Miliusanes, a class of cytotoxic agents from Miliusa sinensis

Hongjie 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. Fong

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

27 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)693-708
Number of pages16
JournalJournal of Medicinal Chemistry
Volume49
Issue number2
DOIs
Publication statusPublished - 26 Jan 2006

Scopus Subject Areas

  • Molecular Medicine
  • Drug Discovery

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