Post-Graduate Program of Pharmacy, Universidade Federal de Santa Catarina, Campus Universitário-Trindade, Florianópolis CEP 8840-970, SC, Brazil.
Department of Chemistry, Universidade Federal de Santa Catarina, Campus Universitário-Trindade, Florianópolis CEP 88040-900, SC, Brazil.
Molecules. 2023 Jan 27;28(3):1243. doi: 10.3390/molecules28031243.
Sesquiterpene lactone (SL) subtypes including hirsutinolide and cadinanolide have a controversial genesis. Metabolites of these classes are either described as natural products or as artifacts produced via the influence of solvents, chromatographic mobile phases, and adsorbents used in phytochemical studies. Based on this divergence, and to better understand the sensibility of these metabolites, different pH conditions were used to prepare semisynthetic SLs and evaluate the anti-inflammatory and antiproliferative activities. Therefore, glaucolide B () was treated with various Brønsted-Lowry and Lewis acids and bases-the same approach was applied to some of its derivatives-allowing us to obtain 14 semisynthetic SL derivatives, 10 of which are hereby reported for the first time. Hirsutinolide derivatives (CC = 5.0 µM; SI = 2.5) and (CC = 11.2 µM; SI = 2.5) and the germacranolide derivative (CC = 3.1 µM; SI = 3.0) revealed significant cytotoxic activity and selectivity against human melanoma SK-MEL-28 cells when compared with that against non-tumoral HUVEC cells. Additionally, compounds and showed strongly reduced interleukin-6 (IL-6) and nitrite (NOx) release in pre-treated M1 macrophages J774A.1 when stimulated with lipopolysaccharide. Despite the fact that hirsutinolide and cadinanolide SLs may be produced via plant metabolism, this study shows that acidic and alkaline extraction and solid-phase purification processes can promote their formation.
倍半萜内酯（SL）亚型包括毛喉萜烯内酯和卡达烯内酯的起源存在争议。这些类别的代谢物要么被描述为天然产物，要么被描述为溶剂、色谱流动相和植物化学研究中使用的吸附剂影响下产生的人工制品。基于这种分歧，并为了更好地了解这些代谢物的敏感性，我们使用不同的 pH 值条件来制备半合成 SL，并评估其抗炎和抗增殖活性。因此，我们用各种布朗斯台德-劳里和路易斯酸和碱处理了格拉醇内酯 B ()，同样的方法也应用于其一些衍生物，使我们能够获得 14 种半合成 SL 衍生物，其中 10 种是首次报道。毛喉萜烯内酯衍生物 （CC = 5.0 µM；SI = 2.5）和 （CC = 11.2 µM；SI = 2.5）和大根香叶烯醇内酯衍生物 （CC = 3.1 µM；SI = 3.0）在人黑色素瘤 SK-MEL-28 细胞中的细胞毒性活性和选择性方面表现出显著的活性，与非肿瘤性 HUVEC 细胞相比。此外，化合物 和 在经脂多糖刺激的 M1 巨噬细胞 J774A.1 中预处理时，显示出强烈减少白细胞介素 6（IL-6）和亚硝酸盐（NOx）的释放。尽管毛喉萜烯内酯和卡达烯内酯 SL 可能是通过植物代谢产生的，但本研究表明，酸性和碱性提取和固相纯化过程可以促进它们的形成。
