School of Pharmaceutical Sciences, University of Geneva, 1211 Geneva 4, Switzerland.
Institute of Pharmaceutical Sciences of Western Switzerland, University of Geneva, 1211 Geneva 4, Switzerland.
J Nat Prod. 2020 Nov 25;83(11):3363-3371. doi: 10.1021/acs.jnatprod.0c00671. Epub 2020 Oct 23.
Twelve new pyridine-4(1)-one derivatives, namely, 8-demethoxywaltherione F (), waltheriones R-V (, , , , and ), 1-methoxywaltherione O (), ()-15-hydroxywaltherione G (), (8)-8-hydroxywaltherione M (), (9,13)-2-hydroxymethylwaltherione C (), (9,10,13)-10-hydroxywaltherione C (), and ()-13-methoxywaltherione V (), as well as melovinone () and 5'-methoxywaltherione A () were isolated from the CHCl extract of the aerial parts of Their chemical structures were determined by means of a comprehensive analysis including H NMR, DEPTQ, HSQC, HMBC, H-H COSY, ROESY, and HRESIMS data. The absolute configurations were assigned via comparison of the experimental and calculated ECD data. In addition, the isolated constituents as well as the known waltheriones M-Q were evaluated for their in vitro antitrypanosomal activity. Compounds , , and as well as waltheriones M, P, and Q showed potent growth inhibition toward with IC values of 2.1, 0.8, 2.1, 1.3, 0.5, and 0.1 μM, respectively, and selectivity indices of >12, >33, >13, 5, 25, and 14. These findings further demonstrate that the waltheriones are a promising class of antichagasic compounds worthy of further investigations.
从美花石斛的地上部分的 CHCl 提取物中分离得到了 12 种新的吡啶-4(1)-酮衍生物，分别为 8-去甲瓦尔特酮 F (), 瓦尔特酮 R-V (,,,, 和 ), 1-甲氧基瓦尔特酮 O (), ()-15-羟基瓦尔特酮 G (), (8)-8-羟基瓦尔特酮 M (), (9,13)-2-羟甲基瓦尔特酮 C (), (9,10,13)-10-羟基瓦尔特酮 C (), 和 ()-13-甲氧基瓦尔特酮 V (), 以及 melovinone () 和 5'-甲氧基瓦尔特酮 A ()。通过综合分析包括 H NMR、DEPTQ、HSQC、HMBC、H-H COSY、ROESY 和 HRESIMS 数据，确定了它们的化学结构。通过比较实验和计算的 ECD 数据，确定了绝对构型。此外，还评估了分离得到的成分以及已知的瓦尔特酮 M-Q 的体外抗锥虫活性。化合物,, 和 以及瓦尔特酮 M、P 和 Q 对 表现出很强的生长抑制作用，IC 值分别为 2.1、0.8、2.1、1.3、0.5 和 0.1 μM，选择性指数分别为>12、>33、>13、5、25 和 14。这些发现进一步表明，瓦尔特酮是一类很有前途的抗恰加斯病化合物，值得进一步研究。
