Small molecule HAT inhibitors are useful tools to unravel the role of
histone acetyltransferases (HATs) in the cell and they also have relevance in oncology. We synthesized a series of 2-acylamino-1-(3- or 4-carboxyphenyl)benzamides 8–19 bearing C6, C8, C10, C12, C14, and C16 acyl chains at the 2-amino position of
2-aminobenzoic acid.
Enzyme inhibition of these compounds was investigated using in vitro PCAF HAT assays. The inhibitory activities of compounds 8–10, 16, and 19 were similar to that of
anacardic acid, and 17 was found to be more active than
anacardic acid at 100 μM. Compounds 11–15 showed the low inhibitory activity on PCAF HAT. The cytotoxicity of the synthesized compounds was evaluated by SRB (
sulforhodamine B) assay against seven human
cancer cell lines: HT-29 (colon), HCT-116 (colon), MDA-231 (breast), A549 (lung), Hep3B (
hepatoma), HeLa (cervical) and Caki (kidney) and one normal cell line (HSF).
Compound 17 was more active than
anacardic acid against human
colon cancer (HCT 116, IC(50): 29.17 μM), human
lung cancer (A549, IC₅₀: 32.09 μM) cell lines. 18 was more active than
anacardic acid against human
colon cancer (HT-29, IC₅₀: 35.49 μM and HCT 116, IC₅₀: 27.56 μM), human
lung cancer (A549, IC₅₀: 30.69 μM), and human
cervical cancer (HeLa, IC₅₀: 34.41 μM) cell lines. The apparent permeability coefficient (P(app), cm/s) values of two compounds (16 and 17) were evaluated as 68.21 and 71.48 × 10⁻⁶ cm/s by Caco-2 cell permeability assay.