Saturated Oxo Fatty Acids (SOFAs): A Previously Unrecognized Class of Endogenous Bioactive Lipids Exhibiting a Cell Growth Inhibitory Activity

Abstract

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.

A Unified Mechanism for the PhCOCOOH‐mediated Photochemical Reactions: Revisiting its Action and Comparison to Known Photoinitiators

“…All other wavelengths (370‐525 nm) ranging over UVA to visible light led to diminished yields (for the power of the lamps see Scheme 8, while for the power of lamps and their photon fluxes, see Supporting Information), which proves the wavelengths at UV range below visible light provide the best platform of irradiation for PhCOCOOH. Very recently, we employed this methodology for the fast and expedient synthesis of oxo‐fatty acids, which exhibited good potency both in cell growth inhibition and in suppressing β‐cell death [29] . We also studied the reaction between 16 and 17 leading to 12OSA 18 (Scheme 8, bottom).…”

“…Very recently, we employed this methodology for the fast and expedient synthesis of oxo-fatty acids, which exhibited good potency both in cell growth inhibition and in suppressing β-cell death. [29] We also studied the reaction between 16 and 17 leading to 12OSA 18 (Scheme 8, bottom). Similarly to above, CFL lamps afforded the highest yield, with 370 nm and sunlight affording a mediocre yield.…”

Identification of an Analytical Method Interference for Perfluorobutanoic Acid in Biological Samples

“…15 We assigned the most likely chemical class to be a saturated oxo-fatty acid (SOFA), which comprised seven of the 149 chemical structures identified in the CompTox Chemicals Dashboard search. SOFAs are involved in fatty acid biosynthesis pathways in all eukaryotes, contain a carboxylic acid group for negative mode ionization, and have been documented in bacteria, 16 yeast, 17 human breath, 18 human plasma, 19 rabbit plasma, 20 and cows and goats milk. 21 Of the several potential dodecanoic SOFAs with the assigned formula C 12 H 22 O 3 , we hypothesize that 3-oxododecanoic acid (Figure 2) is the major chemical interferent observed in the placenta samples, with the interfering 213 → 169 transition occurring as a minor, secondary fragment (Figure 2).…”

“…We assigned the most likely chemical class to be a saturated oxo-fatty acid (SOFA), which comprised seven of the 149 chemical structures identified in the CompTox Chemicals Dashboard search. SOFAs are involved in fatty acid biosynthesis pathways in all eukaryotes, contain a carboxylic acid group for negative mode ionization, and have been documented in bacteria, yeast, human breath, human plasma, rabbit plasma, and cows and goats milk …”

Liquid Chromatography-Mass Spectrometry (LC-MS) Derivatization-Based Methods for the Determination of Fatty Acids in Biological Samples

“…Such uncommon (rare) FAs are usually found at low concentrations; however they exert interesting bioactivities. These uncommon FAs include odd-chain, branched and cyclic FAs [ 8 ] and FAs bearing functional groups such as hydroxy [ 9 , 10 , 11 , 12 ], oxo [ 13 , 14 ], epoxy [ 15 , 16 ] and nitro [ 17 , 18 ].…”