Cytotoxic activity of secondary metabolites from Machaerium isadelphum and structure-activity relationship of machaeriols and machaeridiols

IF 2.1 3区化学 Q2 CHEMISTRY, ORGANIC

Tetrahedron Pub Date : 2025-04-29 DOI:10.1016/j.tet.2025.134694

Ihtiel Benítez-Cortés , Jaime Escalante , Gabriel Navarrete-Vazquez , Leticia González-Maya , Maria Yolanda Rios

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Abstract

Machaerium isadelphum is a species traditionally used in Mexican medicine for the treatment of cancer. In this study, compounds 1–6, isolated from this natural source, are evaluated as potential cytotoxic agents against PC-3 (prostate cancer) and H1299 (lung cancer) cancer‐derived cells. The purification process also led to the isolation of three minor compounds with previously unreported structures (compounds 7–9). The structures of 7–9 are elucidated through the analysis of their spectroscopic and spectrometric data, including 1D and 2D-NMR. Machaeriol A (4) and machaeridiol A (6) exhibited the highest cytotoxic activity. Their structure-activity relationship was further explored by semi-synthesizing nine derivatives (compounds 10–18), which involved homologue alkylation of the hydroxyl groups and modifications to the double bond in the stilbene and monoterpene regions. The cytotoxic activity of these derivatives was compared to that of the natural products 4–6 and 9, revealing that both hydrogenation of the double bonds and its isomerization to the cis form enhanced activity. Compounds 6, 16, and 18 emerged as promising cytotoxic agents.

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石竹次生代谢产物的细胞毒活性及石竹醇与石竹醇的构效关系

石竹是墨西哥传统医学中用于治疗癌症的一种植物。在本研究中，从这种天然来源分离的化合物1-6被评价为潜在的细胞毒性药物，可以抑制PC-3（前列腺癌）和H1299（肺癌）癌源性细胞。该纯化过程还分离出了三个先前未报道结构的次要化合物（化合物7-9）。通过对7-9的光谱和光谱数据的分析，包括一维和二维核磁共振，对其结构进行了阐明。马鲛二醇A(4)和马鲛二醇A(6)的细胞毒活性最高。通过半合成9个衍生物（化合物10-18）进一步探索了它们的构效关系，这些衍生物包括羟基的同源烷基化和对二苯乙烯和单萜烯区域双键的修饰。这些衍生物的细胞毒活性与天然产物4-6和9的细胞毒活性进行了比较，结果表明双键的氢化及其异构化为顺式形式增强了活性。化合物6、16和18是很有前途的细胞毒性药物。

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来源期刊

Tetrahedron 化学-有机化学

CiteScore

3.90

自引率

4.80%

发文量

439

审稿时长

34 days

期刊介绍： Tetrahedron publishes full accounts of research having outstanding significance in the broad field of organic chemistry and its related disciplines, such as organic materials and bio-organic chemistry. Regular papers in Tetrahedron are expected to represent detailed accounts of an original study having substantially greater scope and details than that found in a communication, as published in Tetrahedron Letters. Tetrahedron also publishes thematic collections of papers as special issues and ''Reports'', commissioned in-depth reviews providing a comprehensive overview of a research area.