Synthesis of benzamide derivatives of anacardic acid and their cytotoxic activity

Several benzamide derivatives were synthesized from anacardic acid (1a) which was the product of hydrogenation of the naturally occurring anacardic acid mixture (1a–d), a major constituent of cashew nut shell liquid. Anacardic acid (1a) was first alkylated followed by hydrolysis of the ester to obtain synthones namely, 2-ethoxy-6-pentadecylbenzoic acid (5) and 2-isopropoxy-6-pentadecylbenzoic acid (6). These salicylic acid derivatives were then coupled with a variety of anilines to obtain novel benzamide compounds (7–39). Cytotoxic effect of these synthesized compounds was tested on HeLa cell line of wild type with relatively high expression of p300 and on HCT-15, which is p300 negative. Of all the compounds, 2-isopropoxy-6-pentadecyl-N-pyridin-4-ylbenzamide (27), 2-ethoxy-N-(3-nitrophenyl)-6-pentadecylbenzamide (22) and 2-ethoxy-6-pentadecyl-N-pyridin-4-ylbenzamide (10) were found to be more potent with the respective IC50 values 11.02 μM, 13.55 μM, 15.29 μM on HeLa cell line. Their activities are comparable with garcinol which is a cell permeable histone acetyltransferase (HAT) inhibitor and 10 fold more active than p300 HAT activators so far reported.

Several novel benzamide derivatives were prepared (7–39) from a natural product anacardic acid. The newly synthesized compounds were characterized by IR, NMR and mass spectral studies. These compounds were also screened for their antiproliferative activity against HeLa and HCT-15 cell lines. Preliminary results revealed that compounds 10, 22 and 27 showed promising antiproliferative activity.Figure optionsDownload as PowerPoint slide