Antioxidant and cytotoxic isoprenylated coumarins from Mammea americana.
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 microM, in the three cell lines, respectively) at concentrations comparable to 5-fluorouracil (IC50 = 53.0, 46.1, and 45.1 microM), 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 microM), compounds 1, 5 - 8, and 10, however, had no antioxidant activity (IC50 > 200 microg/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.
Yang
Hui
H
Department of Biological Sciences, Lehman College and The Graduate Center, The City University of New York, Bronx, NY 10468, USA.
Protiva
Petr
P
Gil
Roberto R
RR
Jiang
Bei
B
Baggett
Scott
S
Basile
Margaret J
MJ
Reynertson
Kurt A
KA
Weinstein
I Bernard
IB
Kennelly
Edward J
EJ
D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D000975:Antioxidants / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D001713:Biphenyl Compounds; D045744:Cell Line, Tumor / Q000187:drug effects; D003374:Coumarins / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D005434:Flow Cytometry; D005638:Fruit; D006801:Humans; D020128:Inhibitory Concentration 50; D031252:Mammea; D008517:Phytotherapy; D010851:Picrates / Q000737:chemistry; D010936:Plant Extracts / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D017368:Protein Prenylation; D013329:Structure-Activity Relationship
D000972:Antineoplastic Agents, Phytogenic; D000975:Antioxidants; D001713:Biphenyl Compounds; D003374:Coumarins; D010851:Picrates; D010936:Plant Extracts; C004931:1,1-diphenyl-2-picrylhydrazyl