Center of Natural Sciences and Humanities, Federal University of ABC, SP 09210-580, Santo André, Brazil.
Department of Botany, Institute of Biosciences, University of São Paulo, SP 05508-090, São Paulo, Brazil.
Chem Biodivers. 2021 Oct;18(10):e2100466. doi: 10.1002/cbdv.202100466. Epub 2021 Aug 4.
The hexane extract from aerial parts Baccharis sphenophylla Dusén ex Malme (Asteraceae) displayed activity against amastigote forms of Trypanossoma cruzi and was subjected to chromatographic steps to afford one unreported - 7α-hydroxy-ent-abieta-8(14),13(15)-dien-16,12β-olide (1) and three known diterpenes - ent-kaur-16-en-19-oic acid, (2), grandifloric acid (3), and 15β-tiglinoyloxy-ent-kaur-16-en-19-oic acid (4), two sesquiterpenes - spathulenol (5) and oplopanone (6) - as well as hexacosyl p-coumarate (7). Isolated compounds were characterized by NMR and ESI-HR-MS spectra and were evaluated in vitro for activity against amastigote forms of the parasite T. cruzi - the relevant clinical form in the chronic phase of Chagas disease. In addition, the activity of compounds 1-7 against NCTC cells was evaluated. Compounds 1 and 7 showed effectiveness with EC values of 21.3 and 16.9 μM, respectively. Both compounds also exhibited reduced toxicity against NCTC cells (CC >200 μM) with SI values higher than 9.4 and 11.9. Obtained results suggest that the new ent-abietane diterpene 1 and alkyl coumarate 7 could be used as prototypes for the development of novel and selective semisynthetic derivatives against intracellular forms of T. cruzi.
从 Baccharis sphenophylla Dusén ex Malme（菊科）的地上部分的正己烷提取物显示出对 Trypanossoma cruzi 无鞭毛体形式的活性，并经过色谱步骤得到一种未报告的-7α-羟基-ent-abieta-8(14),13(15)-二烯-16,12β-内酯（1）和三种已知的二萜 - ent-kaur-16-en-19-酸（2），大花酸（3）和 15β- 齐墩果酸-16-烯-19-酸（4），两种倍半萜 - spathulenol（5）和 oplopanone（6）-以及二十六烷酰基对香豆酸（7）。分离得到的化合物通过 NMR 和 ESI-HR-MS 光谱进行表征，并在体外对寄生虫 T. cruzi 的无鞭毛体形式进行了活性评价 - 恰加斯病慢性期的相关临床形式。此外，还评估了化合物 1-7 对 NCTC 细胞的活性。化合物 1 和 7 的 EC 值分别为 21.3 和 16.9μM，表现出有效性。两种化合物对 NCTC 细胞的毒性也降低（CC>200μM），SI 值均高于 9.4 和 11.9。获得的结果表明，新的 ent-abietane 二萜 1 和烷氧基香豆酸 7 可作为开发针对 T. cruzi 细胞内形式的新型和选择性半合成衍生物的原型。
