Center of Excellence for Drug Design and Discovery, Department of Chemistry, National and Kapodistrian University of Athens, Panepistimiopolis, Athens 15771, Greece.
Center of Basic Research, Biomedical Research Foundation of the Academy of Athens, Athens 11527, Greece.
J Med Chem. 2021 May 13;64(9):5654-5666. doi: 10.1021/acs.jmedchem.0c02058. Epub 2021 Apr 21.
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.
发现具有促进人类健康的新型生物活性脂质非常重要。本研究采用“可疑物”和靶向脂质组学液相色谱-高分辨率质谱（LC-HRMS）方法，在人血浆中鉴定出了以前未被识别的氧化脂肪酸，即具有各种长链位置的氧功能的饱和氧脂肪酸（SOFA）。构建了 SOFA 库，应用简单的绿色光化学氢酰化反应作为关键的合成步骤。研究了合成的 SOFA 抑制三种人癌细胞系体外细胞生长的能力。鉴定出四种氧代硬脂酸（OSA）抑制人肺癌 A549 细胞的生长。6OSA 和 7OSA 表现出最高的细胞生长抑制活性，抑制了细胞生长和增殖的关键调节因子 STAT3 和 c-myc 的表达。因此，天然存在的 SOFA 可能在保护人类健康方面发挥作用。
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