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.
Departamento de Química Orgánica, Facultade de Química, Universidade de Vigo, Campus As Lagoas-Marcosende, 36310 Vigo, Spain.
José A
JA
Souto
Mariarosaria
M
Conte
Rosana
R
Alvarez
Angela
A
Nebbioso
Vincenzo
V
Carafa
Lucia
L
Altucci
Angel R
AR
de Lera
D048729:Anacardic Acids / Q000737:chemistry*; D017209:Apoptosis / Q000187:drug effects; D001549:Benzamides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D016195:G2 Phase / Q000187:drug effects; D006098:Granulocytes / Q000187:drug effects; D051548:Histone Acetyltransferases / Q000037:antagonists & inhibitors* / Q000737:chemistry; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D015394:Molecular Structure; D016196:S Phase / Q000187:drug effects; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured; D000077337:Vorinostat; D050880:p300-CBP Transcription Factors / Q000037:antagonists & inhibitors / Q000737:chemistry; D000099224:p300-CBP-Associated Factor
D048729:Anacardic Acids; D001549:Benzamides; D004791:Enzyme Inhibitors; D051548:Histone Acetyltransferases; D006877:Hydroxamic Acids; D000077337:Vorinostat; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor; C088115:anacardic acid