Saturated Oxo Fatty Acids (Sofas): A Previously Unrecognized Class Of Endogenous Bioactive Lipids Exhibiting A Cell Growth Inhibitory Activity

The discovery of novel bioactive lipids that promote human health is of great importance. Combining "suspect" and targeted lipidomic liquid chromatography-high-resolution mass spectrometry (LC-HRMS) approaches, a previously unrecognized class of oxidized fatty acids, the saturated oxo fatty acids (SOFAs), which carry the oxo functionality at various positions of the long chain, was identified in human plasma. A library of SOFAs was constructed, applying a simple green photochemical hydroacylation reaction as the key synthetic step. The synthesized SOFAs were studied for their ability to inhibit in vitro the cell growth of three human cancer cell lines. Four oxostearic acids (OSAs) were identified to inhibit the cell growth of human lung carcinoma A549 cells. 6OSA and 7OSA exhibited the highest cell growth inhibitory potency, suppressing the expression of both STAT3 and c-myc, which are critical regulators of cell growth and proliferation. Thus, naturally occurring SOFAs may play a role in the protection of human health.