Institute of Organic Chemistry and Biochemistry, Czech Academy of Sciences, 166 10 Prague, Czech Republic.
Institute of Experimental Medicine, Czech Academy of Sciences, 142 20 Prague, Czech Republic.
Molecules. 2024 Jul 11;29(14):3289. doi: 10.3390/molecules29143289.
Trilobolide and its analogues belong to the guaianolide type of sesquiterpene lactones, which are characteristic and widely distributed within the families Asteraceae and Apiaceae. Certain guaianolides are receiving continuously increasing attention for their promising sarco-endoplasmic reticulum Ca-ATPase (SERCA)-inhibitory activity. However, because of their alkylation capabilities, they are generally toxic. Therefore, the search for compounds with significant immunobiological properties but with decreased cytotoxicities suitable for use in immune-based pharmacotherapy is ongoing. Therefore, we extended our previous investigation of the immunobiological effects of trilobolide to a series of structurally related guaianolides and germacranolides. To evaluate the relationship, we tested a series of selected derivatives containing α-methyl lactone or exomethylene lactone ring. For a wider comparison, we also included some of their glycosidic derivatives. We assessed the in vitro immunobiological effects of the tested compounds on nitric oxide (NO) production, cytokine secretion, and prostaglandin E2 (PGE2) release by mouse peritoneal cells, activated primarily by lipopolysaccharide (LPS), and evaluated their viability. The inhibitory effects of the apparently most active substance, 8-deoxylactucin, seem to be the most promising.
三萜内酯及其类似物属于愈创木烷型倍半萜内酯，在菊科和伞形科中广泛分布，具有特征性。某些愈创木烷型倍半萜内酯由于具有肌浆内质网 Ca-ATP 酶（SERCA）抑制活性而受到持续关注。然而，由于其烷基化能力，它们通常具有毒性。因此，人们一直在寻找具有显著免疫生物学特性但细胞毒性降低的化合物，适用于免疫为基础的药物治疗。因此，我们将三萜内酯的免疫生物学效应的先前研究扩展到一系列结构相关的愈创木烷型倍半萜内酯和大根香叶烯型倍半萜内酯。为了评估这种关系，我们测试了一系列含有α-甲基内酯或外亚甲基内酯环的选定衍生物。为了进行更广泛的比较，我们还包括了它们的一些糖苷衍生物。我们评估了测试化合物对由脂多糖（LPS）主要激活的小鼠腹腔细胞中一氧化氮（NO）产生、细胞因子分泌和前列腺素 E2（PGE2）释放的体外免疫生物学效应，并评估了它们的活力。显然最活跃的物质 8-去氧乳香酸的抑制作用似乎最有前途。
