The field of bioactive lipids is
ever expanding with discoveries
of novel lipid molecules that promote human health. Adopting a lipidomic-assisted
approach, two new families of previously unrecognized saturated hydroxy
fatty acids (SHFAs), namely, hydroxystearic and hydroxypalmitic acids,
consisting of isomers with the hydroxyl group at different positions,
were identified in milk. Among the various regio-isomers synthesized,
those carrying the hydroxyl at the 7- and 9-positions presented growth
inhibitory activities against various human cancer cell lines, including
A549, Caco-2, and SF268 cells. In addition, 7- and 9-hydroxystearic
acids were able to suppress β-cell apoptosis induced by proinflammatory
cytokines, increasing the possibility that they can be beneficial
in countering autoimmune diseases, such as type 1 diabetes. 7-(R)-Hydroxystearic acid exhibited the highest potency both
in cell growth inhibition and in suppressing β-cell death. We
propose that such naturally occurring SHFAs may play a role in the
promotion and protection of human health.
The lipidome of royal jelly (RJ) consists of medium-chained (8–12 carbon atoms) free fatty acids. We present herein a liquid chromatography-high resolution mass spectrometry (HRMS) method that permits the determination of RJ fatty acids and at the same time the detection of suspect fatty acids. The method allows for the direct quantification of seven free fatty acids of RJ, avoiding any derivatization step. It was validated and applied in seven RJ samples, where the major RJ fatty acid trans-10-hydroxy-2-decenoic acid (10-HDA) was found to vary from 0.771 ± 0.08 to 0.928 ± 0.04 g/100 g fresh RJ. Four additional suspect fatty acids were simultaneously detected taking advantage of the HRMS detection.
Introduction
Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has caused the devastating pandemic named coronavirus disease 2019 (COVID-19). Unfortunately, the discovery of antiviral agents to combat COVID-19 is still an unmet need. Transmembrane serine protease 2 (TMPRSS2) is an important mediator in viral infection and thus, TMPRRS2 inhibitors may be attractive agents for COVID-19 treatment.
Areas covered
This review article discusses the role of TMPRSS2 in SARS-CoV-2 cell entry and summarizes the inhibitors of TMPRSS2 and their potential anti-SARS activity. Two known TMPRSS2 inhibitors, namely camostat and nafamostat, approved drugs for the treatment of pancreatitis, are under clinical trials as potential drugs against COVID-19.
Expert opinion
Due to the lack of the crystal structure of TMPRSS2, homology models have been developed to study the interactions of known inhibitors, including repurposed drugs, with the enzyme. However, novel TMPRSS2 inhibitors have been identified through high-throughput screening, and appropriate assays studying their
in vitro
activity have been set up. The discovery of TMPRSS2ʹs crystal structure will facilitate the rational design of novel inhibitors and
in vivo
studies and clinical trials will give a clear answer if TMPRSS2 inhibitors could be a new weapon against COVID-19.
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.
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