Cytotoxic flavaglines and bisamides from Aglaia edulis.
Two new cyclopenta[b]benzofurans, aglaroxin A 1-O-acetate (2) and 3'-methoxyaglaroxin A 1-O-acetate (3), a new benzo[b]oxepine, 19,20-dehydroedulisone A (4), and five new cyclopenta[bc]benzopyrans, edulirin A (5), edulirin A 10-O-acetate (6), 19,20-dehydroedulirin A (7), isoedulirin A (8), and edulirin B (9), were isolated from the bark of Aglaia edulis, along with one known cyclopenta[b]benzofuran, aglaroxin A (1). Additionally, four new amides, aglamides A-D (10-13), as well as three known compounds, aglalactone, scopoletin, and 5-hydroxy-3,6,7,4'-tetramethoxyflavone, were isolated from the leaves and/or twigs of this species. The structures of the new compounds (2-13) were elucidated by interpretation of their spectroscopic data. All isolates obtained in this study were evaluated for cytotoxicity against both several human cancer cell lines (Lu1, LNCaP, and MCF-7) and a nontumorigenic (HUVEC) cell line. Among these isolates, the cyclopenta[b]benzofurans (1-3) exhibited potent in vitro cytotoxic activity (ED50 range 0.001 to 0.8 microg/mL). Aglaroxin A 1-O-acetate (2) was further evaluated in the in vivo P388 lymphocytic leukemia model, by intraperitoneal injection, but found to be inactive in this model.
Kim
Soyoung
S
Program for Collaborative Research in the Pharmaceutical Sciences and Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois at Chicago, Chicago, IL 60612, USA.
Chin
Young-Won
YW
Su
Bao-Ning
BN
Riswan
Soedarsono
S
Kardono
Leonardus B S
LB
Afriastini
Johar J
JJ
Chai
Heebyung
H
Farnsworth
Norman R
NR
Cordell
Geoffrey A
GA
Swanson
Steven M
SM
Kinghorn
A Douglas
AD
D000577:Amides / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D001572:Benzofurans / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007214:Indonesia; D007941:Leukemia P388; D029582:Meliaceae / Q000737:chemistry*; D051379:Mice; D023421:Models, Animal; D024301:Plant Bark / Q000737:chemistry; D018515:Plant Leaves / Q000737:chemistry; D018547:Plant Stems / Q000737:chemistry; D010946:Plants, Medicinal / Q000737:chemistry*
D000577:Amides; D000972:Antineoplastic Agents, Phytogenic; D001572:Benzofurans