Twelve new pyridine-4(1H)-one derivatives, namely, 8-demethoxywaltherione F (1), waltheriones R–V (2, 6, 7, 10, and 11), 1-methoxywaltherione O (3), (S)-15-hydroxywaltherione G (4), (8R)-8-hydroxywaltherione M (5), (9S,13S)-2-hydroxymethylwaltherione C (8), (9S,10S,13S)-10-hydroxywaltherione C (9), and (S)-13-methoxywaltherione V (12), as well as melovinone (13) and 5′-methoxywaltherione A (14) were isolated from the CH₂Cl₂ extract of the aerial parts of Waltheria indica. Their chemical structures were determined by means of a comprehensive analysis including ¹H NMR, DEPTQ, HSQC, HMBC, ¹H–¹H 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 2, 5, and 7 as well as waltheriones M, P, and Q showed potent growth inhibition toward Trypanosoma cruzi with IC₅₀ 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.

中文翻译：

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Pyridine-4(1H)-one 来自 Waltheria indica 的生物碱作为抗锥虫药

12 种新的吡啶-4(1 H )-one 衍生物，即 8-脱甲氧基waltherione F ( 1 )、waltheriones R–V ( 2、6、7、10和11 )、1-甲氧基waltherione O ( 3 )、 ( S）-15- hydroxywaltherione G（4），（8 - [R）-8- hydroxywaltherione M（5），（9小号，13小号）-2- hydroxymethylwaltherione C（8），（9小号，10小号，13小号） - 10-羟基瓦尔三酮 C ( 9 ) 和 ( S从Waltheria indica地上部分的CH ₂ Cl ₂提取物中分离出) -13-甲氧基瓦尔瑟酮V ( 12 ) 以及美洛维酮( 13 ) 和5'-甲氧基瓦尔瑟酮A ( 14 ) 。它们的化学结构是通过综合分析确定的，包括¹ H NMR、DEPTQ、HSQC、HMBC、¹ H– ¹ H COSY、ROESY 和 HRESIMS 数据。通过比较实验和计算的 ECD 数据分配绝对配置。此外，还评估了分离的成分以及已知的 waltheriones M-Q 的体外抗锥虫活性。化合物2 ,5和7以及 waltheriones M、P 和 Q 对克氏锥虫显示出有效的生长抑制作用，IC ₅₀值分别为 2.1、0.8、2.1、1.3、0.5和 0.1 μM，选择性指数 >12，> 33、>13、5、25 和 14。这些发现进一步表明，waltheriones 是一类有前途的抗恰加斯化合物，值得进一步研究。