Planta Med 2005; 71(9): 852-860
DOI: 10.1055/s-2005-871257
Original Paper
Natural Product Chemistry
© Georg Thieme Verlag KG Stuttgart · New York

Antioxidant and Cytotoxic Isoprenylated Coumarins from Mammea americana

Hui Yang1 , Petr Protiva2 , Roberto R. Gil3 , Bei Jiang2 , Scott Baggett1 , Margaret J. Basile4 , Kurt A. Reynertson1 , I. Bernard Weinstein2 , Edward J. Kennelly1
  • 1Department of Biological Sciences, Lehman College and The Graduate Center, The City University of New York, Bronx, NY, USA
  • 2Department of Medicine, Columbia University Medical Center, New York, NY, USA
  • 3Department of Chemistry, Carnegie Mellon University, Pittsburgh, PA, USA
  • 4Department of Neurology, University of Miami School of Medicine, Miami, FL, USA
Further Information

Publication History

Received: November 3, 2004

Accepted: March 30, 2005

Publication Date:
19 September 2005 (online)

Abstract

Antioxidant-guided fractionation of Mammea americana L. seeds resulted in the identification of three new isoprenylated coumarins, mammea B/BA hydroxycyclo F (1), mammea E/BC (2), and mammea E/BD (3). In addition, twelve known isoprenylated coumarins, mammea A/AA (4), mammea A/AA cyclo D (5), mammea A/AA cyclo F (6), mammea A/AC cyclo D (7), mammea A/AD cyclo D (8), mammea B/BA (9), mammea B/BA cyclo F (10), mammea B/BB (11), mammea B/BC (12), mammea B/BD (13), mammea E/BA (14), and mammea E/BB (15), as well as two known flavanols, (+)-catechin (16) and (-)-epicatechin (17) were identified. The fifteen isoprenylated coumarins were screened for their cytotoxicity in the SW-480, HT-29, and HCT-116 human colon cancer cell lines and antioxidant capacities in the DPPH (1,1-diphenyl-2-picrylhydrazyl) free-radical assay. Compounds 1 - 15 exhibited significant cytotoxic activities in the SW-480, HT-29, and HCT-116 human colon cancer cell lines (IC50 ranges 13.9 - 88.1, 11.2 - 85.3, and 10.7 - 76.7 μM, in the three cell lines, respectively) at concentrations comparable to 5-fluorouracil (IC50 = 53.0, 46.1, and 45.1 μM), a drug frequently used for human colon cancer treatment. Compounds 2 - 4, 9, and 11 - 15 displayed high antioxidant activity in the DPPH assay (IC50 range 86 - 135 μM ), compounds 1, 5 - 8, and 10, however, had no antioxidant activity (IC50 > 200 μg/mL) in the DPPH assay. The results of these assays were used to study the structure-activity relationships for this class of compounds. In the SW-480 cell line, the three new coumarins, 1 - 3, also exhibited dose-dependent increases in sub-diploid cells by flow cytometry, indicating that they induce apoptosis.

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Dr. Edward J. Kennelly

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