González-Cardenete Miguel A, Rivas Fatima, Basset Rachel, Stadler Marco, Hering Steffen, Padrón José M, Zaragozá Ramón J, Dea-Ayuela María Auxiliadora
Instituto de Tecnología Química (UPV-CSIC), Universitat Politècnica de València-Consejo Superior de Investigaciones Científicas, Avda. de los Naranjos s/n, 46022 Valencia, Spain.
Department of Chemical Biology and Therapeutics, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
Antibiotics (Basel). 2021 Feb 12;10(2):184. doi: 10.3390/antibiotics10020184.
The abietane-type diterpenoids are significant bioactive compounds exhibiting a varied range of pharmacological properties. In this study, the first synthesis and biological investigation of the new abietane-diterpenoid (+)-4-epi-liquiditerpenoid acid (8a) together with several of its analogs are reported. The compounds were generated from the readily available methyl callitrisate (7), which was obtained from callitrisic acid present in Moroccan Sandarac resin. A biological evaluation was conducted to determine the effects of the different functional groups present in these molecules, providing basic structure-activity relationship (SAR) elements. In particular, the ferruginol and sugiol analogs compounds - were characterized by the presence of a phenol moiety, higher oxidization states at C-7 (ketone), and the hydroxyl, methyl ester or free carboxylic acid at C19. The biological profiling of these compounds was investigated against a panel of six human solid tumor cell lines (HBL-100, A549, HeLa, T-47D, SW1573 and WiDr), four parasitic species (, , and ) and two malaria strains (3D7 and K1). Furthermore, the capacity of the compounds to modulate gamma-aminobutyric acid type A (GABA) receptors (αβγ) is also described. A comparison of the biological results with those previously reported of the corresponding C18-functionalized analogs was conducted.
枞酸型二萜类化合物是具有多种药理特性的重要生物活性化合物。在本研究中，报道了新型枞酸型二萜类化合物（+）-4-表-液体二萜酸（8a）及其几种类似物的首次合成和生物学研究。这些化合物由易于获得的甲基愈创木酚（7）制备而成，甲基愈创木酚是从摩洛哥山达脂树脂中的愈创木酸获得的。进行了生物学评价以确定这些分子中存在的不同官能团的作用，提供基本的构效关系（SAR）要素。特别是，铁锈醇和苏乔醇类似物化合物的特征在于存在酚部分、C-7处较高的氧化态（酮）以及C19处的羟基、甲酯或游离羧酸。针对一组六种人类实体瘤细胞系（HBL-100、A549、HeLa、T-47D、SW1573和WiDr）、四种寄生虫物种（、、和）以及两种疟疾菌株（3D7和K1）对这些化合物的生物学特性进行了研究。此外，还描述了这些化合物调节A型γ-氨基丁酸（GABA）受体（αβγ）的能力。将生物学结果与先前报道的相应C18官能化类似物的结果进行了比较。
