Miliusanes, a class of cytotoxic agents from Miliusa sinensis.
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 C(18) 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 gamma-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.
Zhang
Hong-Jie
HJ
Program for Collaborative Research in the Pharmaceutical Sciences, Department of Medicinal Chemistry and Pharmacognosy, University of Illinois at Chicago, Illinois 60612, USA. zhanghj@uic.edu
Ma
Cuiying
C
Nguyen
Van Hung
VH
Nguyen
Manh Cuong
MC
Tan
Ghee Teng
GT
Santarsiero
Bernard D
BD
Mesecar
Andrew D
AD
Soejarto
D Doel
DD
Pezzuto
John M
JM
Fong
Harry H S
HH
D015107:4-Butyrolactone / Q000031:analogs & derivatives / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D029061:Annonaceae / Q000737:chemistry*; D000970:Antineoplastic Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D045744:Cell Line, Tumor; D018360:Crystallography, X-Ray; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007783:Lactones / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D015394:Molecular Structure; D010936:Plant Extracts / Q000494:pharmacology; D018514:Plant Structures / Q000737:chemistry; D013141:Spiro Compounds / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology
D000970:Antineoplastic Agents; D007783:Lactones; D010936:Plant Extracts; D013141:Spiro Compounds; D015107:4-Butyrolactone