Souto José A, Conte Mariarosaria, Alvarez Rosana, Nebbioso Angela, Carafa Vincenzo, Altucci Lucia, de Lera Angel R
Departamento de Química Orgánica, Facultade de Química, Universidade de Vigo, Campus As Lagoas-Marcosende, 36310 Vigo, Spain.
ChemMedChem. 2008 Sep;3(9):1435-42. doi: 10.1002/cmdc.200800096.
A group of benzamides related to anacardic acid amide CTPB with alkyl chains of defined length were prepared by a five-step sequence starting from 2,6-dihydroxybenzoic acid, and their activities were compared with those reported for the HAT inhibitor anacardic acid (AA). The subset of 4-cyano-3-trifluoromethylphenylbenzamides with shorter chains exhibited activities similar to that of AA, as they behaved as human p300 inhibitors, induced a decrease in histone acetylation levels in immortalized HEK cells, and counteracted the action of the HDAC inhibitor SAHA in MCF7 breast cancer cells. Moreover, an analogue with the shortest alkyl chain induced significant apoptosis at 50 microM in U937 leukemia cells.
从2,6 - 二羟基苯甲酸开始，通过五步反应制备了一组与具有特定长度烷基链的腰果酰胺CTPB相关的苯甲酰胺，并将它们的活性与已报道的组蛋白乙酰转移酶（HAT）抑制剂腰果酸（AA）的活性进行了比较。具有较短链的4 - 氰基 - 3 - 三氟甲基苯基苯甲酰胺子集表现出与AA相似的活性，因为它们作为人p300抑制剂，可导致永生化HEK细胞中组蛋白乙酰化水平降低，并抵消HDAC抑制剂SAHA在MCF7乳腺癌细胞中的作用。此外，具有最短烷基链的类似物在50 microM浓度下可诱导U937白血病细胞发生显著凋亡。
