Batista Pedro Henrique J, de Lima Karísia Sousa B, Pinto Francisco das Chagas L, Tavares Juliane L, de A Uchoa Daniel E, Costa-Lotufo Letícia V, Rocha Danilo D, Silveira Edilberto R, Bezerra Antonio Marcos E, Canuto Kirley M, Pessoa Otília Deusdenia L
Departamento de Química Orgânica e Inorgânica, Centro de Ciências, Universidade Federal do Ceará, 60021-970, Fortaleza, CE, Brazil.
Departamento de Farmacologia, Universidade de São Paulo, 05508-900, São Paulo, SP, Brazil.
Phytochemistry. 2016 Oct;130:321-7. doi: 10.1016/j.phytochem.2016.07.003. Epub 2016 Aug 4.
Seven withanolides, including four previously unknown, were isolated from the acetone and ethanol extracts of cultivated specimens of Acnistus arborescens. These four compounds were identified as rel-(18R,22R)-5β,6β:18β,20-diepoxy-3β,18α-dimethoxy-4β-hydroxy-1-oxowith-24-enolide, rel-(20R,22R)-5β,6β-epoxy-4β,16α,20-trihydroxy-1-oxowitha-2,24dienolide, rel-(20R,22R)-16α-acetoxy-6α-chloro-4β,5β,20-trihydroxy-1-oxowitha-2,24-dienolide and rel-(20R,22R)-16α-acetoxy-20-hydroxy-1-oxowitha-2,5,24-trienolide. Their structures were elucidated by interpretation of spectroscopic data (1D and 2D NMR), HRESIMS experiments and comparison with published data for similar compounds. Cytotoxicity of the isolated compounds was evaluated against a panel of four tumor cell lines (HL-60, HCT-116, SF-268 and PANC-1). Withanolide D was the most active, with an IC50 value in the range of 0.3-1.7 μM, rel-(18R,22R)-5β,6β:18β,20-diepoxy-3β,18α-dimethoxy-4β-hydroxy-1-oxowith-24-enolide and rel-(20R,22R)-5β,6β-epoxy-4β,16α,20-trihydroxy-1-oxowitha-2,24dienolide were moderately active, while all the others were non-cytotoxic.
从栽培的乔木状阿尼克斯特草（Acnistus arborescens）标本的丙酮和乙醇提取物中分离出7种睡茄内酯，其中包括4种此前未知的化合物。这4种化合物被鉴定为rel-(18R,22R)-5β,6β:18β,20-二环氧-3β,18α-二甲氧基-4β-羟基-1-氧代-威-24-烯醇内酯、rel-(20R,22R)-5β,6β-环氧-4β,16α,20-三羟基-1-氧代-威-2,24-二烯醇内酯、rel-(20R,22R)-16α-乙酰氧基-6α-氯-4β,5β,20-三羟基-1-氧代-威-2,24-二烯醇内酯和rel-(20R,22R)-16α-乙酰氧基-20-羟基-1-氧代-威-2,5,24-三烯醇内酯。通过对光谱数据（一维和二维核磁共振）的解读、高分辨电喷雾电离质谱实验以及与类似化合物的已发表数据进行比较，阐明了它们的结构。对分离出的化合物针对4种肿瘤细胞系（HL-60、HCT-116、SF-268和PANC-1）进行了细胞毒性评估。睡茄内酯D活性最强，半数抑制浓度（IC50）值在0.3 - 1.7 μM范围内，rel-(18R,22R)-5β,6β:18β,20-二环氧-3β,18α-二甲氧基-4β-羟基-1-氧代-威-24-烯醇内酯和rel-(20R,22R)-5β,6β-环氧-4β,16α,20-三羟基-1-氧代-威-2,24-二烯醇内酯活性中等，而其他所有化合物均无细胞毒性。
