Interference by naturally occurring fatty acids in a noncellular enzyme-based aromatase bioassay.
Natural product drug discovery efforts frequently utilize noncellular screening assays. Fatty acids are commonly found in natural product extracts, and some have been shown to interfere with noncellular assays. Several pure fatty acids were tested using a noncellular aromatase assay, with the unsaturated analogues showing strong inhibitory activity, while the saturated analogues were inactive. Unsaturated fatty acids were further tested against SK-BR-3 hormone-independent human breast cancer cells that overexpress aromatase and were found to be inactive. In natural product screening efforts, especially using plant seeds, it is recommended that extracts active in noncellular bioassays should be dereplicated for the presence of fatty acids prior to bioassay-guided fractionation.
Balunas
Marcy J
MJ
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.
Su
Bin
B
Landini
Serena
S
Brueggemeier
Robert W
RW
Kinghorn
A Douglas
AD
D001141:Aromatase / Q000378:metabolism*; D001688:Biological Products / Q000737:chemistry* / Q000378:metabolism*; D001943:Breast Neoplasms; D005227:Fatty Acids / Q000737:chemistry* / Q000378:metabolism*; D005260:Female; D006801:Humans; D008861:Microsomes / Q000201:enzymology; D010920:Placenta / Q000201:enzymology; D014407:Tumor Cells, Cultured
D001688:Biological Products; D005227:Fatty Acids; D001141:Aromatase