Faculdade de Farmácia, Departamento de Produtos Farmacêuticos, Universidade Federal de Minas Gerais, Av Antônio Carlos, 6627 CEP 31.270-901 Belo Horizonte, MG, Brazil.
Molecules. 2013 Aug 16;18(8):9919-32. doi: 10.3390/molecules18089919.
The aim of the present work was to carry out a bioguided isolation of antiviral chemical constituents from an ethanol extract of leaves from Arrabidaea pulchra (Cham.) Sandwith (EEAPL) that had shown in vitro activity in a previous screening using DNA and RNA viruses. The activity of EEPAL was evaluated against the DNA viruses Human herpesvirus 1 (HSV-1) and Vaccinia virus Western Reserve (VACV-WR) as well as against the RNA viruses Murine encephalomyocarditis virus (EMCV), and Dengue virus 2 (DENV-2) by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) colorimetric assay. Cytotoxicity was determined in LLCMK2 and Vero cells and the Selectivity Indexes (SI) were calculated. The most potent effect was observed against DENV-2 (EC50 46.8 ± 1.6 µg mL(-1); SI 2.7). For HSV-1 and VACV-WR EC50 values > 200 µg mL(-1) were determined, while no inhibition of the cytopathic effect was observed with EMCV. Bioguided fractionation of EEAPL by partition between immiscible solvents followed by chromatography over a Sephadex LH20 column afforded two arylpropanoid glycosides, verbascoside (AP 1) and caffeoylcalleryanin (AP 2), along with a terpenoid, ursolic acid (AP 3). AP 1 and AP 3 exhibited similar anti-DENV-2 profiles, with SI values of 3.8 and 3.1, respectively, while AP 2 was the most effective anti-DENV-2 constituent, with a SI of 20.0. Our results show that A. pulchra leaves ethanol extract (EEAPL) affords compounds with antiviral activity, mainly against DENV-2.
本工作的目的是从先前使用 DNA 和 RNA 病毒进行的体外活性筛选中表现出活性的 Arrabidaea pulchra(Cham.)Sandwith 叶的乙醇提取物(EEAPL)中进行生物导向分离抗病毒化学成分。通过 3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴化物(MTT)比色法评估 EEAPL 对 DNA 病毒人疱疹病毒 1(HSV-1)和牛痘病毒西部储备(VACV-WR)以及 RNA 病毒鼠脑炎心肌炎病毒(EMCV)和登革热病毒 2(DENV-2)的活性。在 LLCMK2 和 Vero 细胞中测定细胞毒性,并计算选择性指数(SI)。观察到对 DENV-2 的最强作用(EC50 46.8 ± 1.6 µg mL(-1);SI 2.7)。对于 HSV-1 和 VACV-WR,确定 EC50 值> 200 µg mL(-1),而 EMCV 没有观察到细胞病变效应的抑制。通过不混溶溶剂之间的分配和 Sephadex LH20 柱层析对 EEAPL 进行生物导向分级分离,得到两种芳基丙糖苷,毛蕊花糖苷(AP 1)和咖啡酰根皮素(AP 2),以及一种萜烯,熊果酸(AP 3)。AP 1 和 AP 3 表现出相似的抗 DENV-2 谱,SI 值分别为 3.8 和 3.1,而 AP 2 是最有效的抗 DENV-2 成分,SI 值为 20.0。我们的结果表明,A. pulchra 叶乙醇提取物(EEAPL)提供具有抗病毒活性的化合物,主要针对 DENV-2。