New anacardic acid-inspired benzamides: histone lysine acetyltransferase activators.
A series of N-(4-cyano-3-trifluoromethyl-phenyl)-2-ethoxy-6-alkyl (and alkenyl) benzamides related to the anacardic acid derivative CTPB have been prepared from 2,6-dihydroxybenzoic acid with a Suzuki coupling and addition of the anion of 4-cyano-3-trifluoromethylphenylamine to a benzodioxinone as the key steps. In U937 cells, these analogues, in particular 7 c, 7 d, 7 f and 7 j, induced cell-cycle arrest in the G1 phase, caused apoptosis in about 20 % of the cells, and increased the acetylation levels of H3. These activities correlate with the enzymatic activation of histone lysine acetyltransferases (KATs): CBP and PCAF.
Souto
José A
JA
Departamento de Química Orgánica, Facultade de Química, Universidade de Vigo, Campus As Lagoas-Marcosende, 36310 Vigo, Spain.
Benedetti
Rosaria
R
Otto
Katharina
K
Miceli
Marco
M
Alvarez
Rosana
R
Altucci
Lucia
L
de Lera
Angel R
AR
D000107:Acetylation; D048729:Anacardic Acids / Q000737:chemistry*; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D017209:Apoptosis; D001549:Benzamides / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D045744:Cell Line, Tumor; D016193:G1 Phase; D051548:Histone Acetyltransferases / Q000737:chemistry* / Q000378:metabolism; D006801:Humans
D048729:Anacardic Acids; D000970:Antineoplastic Agents; D001549:Benzamides; C088115:anacardic acid; D051548:Histone Acetyltransferases