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 IC(50) values 11.02 microM, 13.55 microM, 15.29 microM 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.
Chandregowda
Venkateshappa
V
Vittal Mallya Scientific Research Foundation, P.O. Box 406, K.R. Road, Bangalore 560004, Karnataka, India.
Kush
Anil
A
Reddy
Goukanapalli Chandrasekara
GC
D048729:Anacardic Acids / Q000737:chemistry*; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001549:Benzamides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006367:HeLa Cells; D006801:Humans; D015394:Molecular Structure; D013237:Stereoisomerism
D048729:Anacardic Acids; D000970:Antineoplastic Agents; D001549:Benzamides; C088115:anacardic acid; C037689:benzamide