Departmento de Productos Naturales, Instituto de Química, Universidad Nacional Autónoma de México. C. Exterior, C. Universitaria, Ciudad de México, Coyoacán, 04510 DCMX, México.
Departamento de Biología Molecular y Biotecnología, Instituto de Investigaciones Biomédicas., Universidad Nacional Autónoma de México. C. Exterior, C. Universitaria, Ciudad de México, Coyoacán, 04510 DCMX, México.
Chem Biodivers. 2024 May;21(5):e202301346. doi: 10.1002/cbdv.202301346. Epub 2024 Mar 29.
It was found that Argentatins A and B triterpenoids make up approximately 20-30 % of the waste resin produced from the industrial processes to isolate rubber from P. argentatum. We have developed an efficient protocol for synthesizing cycloartane-16β-ol derivatives by opening the oxepane ring of argentatin B acetate (2) with BF-OEt. Although three new cycloartenol derivatives showed high cytotoxicity against PC-3 and HCT-15 cancer cell lines, nevertheless, the best results were obtained for (16β,24R) -(16,24-epoxy-cycloartan-2(1H)-ylidene) acetate (14), compound with intact oxepane ring. These results indicate that the substituents in the argentatin nucleus and a side chain account for the cytotoxic activity. However, according to the selectivity index (SI), 14 did not show selectivity activity to cancer cell lines over the HaCat noncancerous cell line. The compound 3β,16β-Dihydroxy-cycloartan-24-one (5), synthesized by oxepane opening, demonstrated high cytotoxic activity to cancer cell lines and showed a remarkable selectivity to cancer cell lines over the noncancerous ones. These results suggest that 5 could lead to the development of new anticancer compounds.
研究发现，银胶菊工业提取橡胶过程中产生的废树脂中约有 20-30%为银胶菊醇萜类化合物。我们开发了一种高效的方法，通过 BF-OEt 打开银胶菊醇 B 乙酸酯（2）的环氧乙烷环，合成环阿尔廷醇衍生物。尽管三种新型的环阿尔廷醇衍生物对 PC-3 和 HCT-15 癌细胞系表现出高细胞毒性，但具有完整环氧乙烷环的（16β,24R）-（16,24-环氧-环阿尔廷-2(1H)-亚基）乙酸酯（14）表现出最佳的结果。这些结果表明，银胶菊核中的取代基和侧链是细胞毒性活性的原因。然而，根据选择性指数（SI），14 对癌细胞系没有表现出对非癌细胞系 HaCat 的选择性活性。通过环氧乙烷开环合成的 3β,16β-二羟基-环阿尔廷-24-酮（5）对癌细胞系表现出高细胞毒性活性，并对癌细胞系表现出显著的选择性。这些结果表明 5 可能会导致新的抗癌化合物的开发。
