Synthesis of benzamides related to anacardic acid and their histone acetyltransferase (HAT) inhibitory activities.

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.