LEXINGTON, Mass.—While natural products are considered a good source of chemical diversity in drug discovery, they are typically plagued by solubility issues and extract colorants interfere with many assays. To get around this problem, researchers at Cubist Pharmaceuticals recently adapted the alamarBlue (AB) fluorescence assay to develop a high-throughput cell-based screen.
As the researchers explained in a poster presented at the recent SBS conference, AB is a metabolic indicator dye that is non-fluorescent when oxidized but changes to pink and becomes fluorescent when reduced by metabolic enzymes. As such, they used the dye as cell viability indicator to screen the inhibitory effects of a panel of natural products against a series of wild-type and drug-resistant microbes.
In a 384-well format, the researchers noted the AB assay generated comparable minimum inhibitory concentration levels for several known antimicrobials when compared to a standard turbidometric assay. They then screened a panel of natural products for efficacy and achieved a hit rate of 2-5 percent, identifying 15 known classes of antimicrobial compounds and 15 compounds not previously identified as having antimicrobial activity.