Instituto de Química, Universidade de Brasília, Campus Darcy Ribeiro, Brasilia, Brazil.
Eur J Med Chem. 2010 Aug;45(8):3480-9. doi: 10.1016/j.ejmech.2010.05.015. Epub 2010 May 12.
This work is part of a large program, which seeks to discover new antitumor isobenfuranones designed from anacardic acids. The synthetic strategy for the construction of the title compounds takes into consideration the use of inexpensive anacardic acids (2), the major natural cashew (Anacardium occidentale) nut-shell phenolic lipid, and features one-pot construction of fused-ring aromatic gamma-lactones, phthalides. The cytotoxicity screening in different human cancer cell lines (HL-60 leukemia, SF295 glioblastoma and MDA-MB435 melanoma) by the MTT assay showed that acyclic precursor (6), and isobenfuranones (1a and 1b) are active compounds. Interestingly, 1a exhibits significant antiproliferative effect against HL-60 cells and moderate activity against SF295 and MDA-MB435 cell lines. Analysis of mechanisms involved in the cytotoxic activity showed that active compounds were leading to DNA damage, triggering apoptosis or necrosis induction.
这项工作是一个大型项目的一部分，该项目旨在发现新的抗肿瘤异苯并呋喃酮，这些化合物是从腰果酚酸设计而来的。标题化合物的合成策略考虑了使用廉价的腰果酚酸（2），这是腰果（Anacardium occidentale）坚果壳中主要的天然酚类脂质，并采用一锅法构建了稠合环芳香γ-内酰胺、邻苯二甲酸酯。MTT 法在不同的人癌细胞系（HL-60 白血病、SF295 神经胶质瘤和 MDA-MB435 黑色素瘤）中的细胞毒性筛选表明，无环前体（6）和异苯并呋喃酮（1a 和 1b）是活性化合物。有趣的是，1a 对 HL-60 细胞表现出显著的抗增殖作用，对 SF295 和 MDA-MB435 细胞系也具有中等活性。对细胞毒性活性涉及的机制的分析表明，活性化合物导致 DNA 损伤，引发细胞凋亡或坏死诱导。
