Design, synthesis and biological evaluation of novel compounds with conjugated structure as anti-tumor agents.
A series of hydroxamic acids with conjugated structure was designed and synthesized to explore the possible HDAC subtype selectivity by testing these compounds against recombinant human HDAC1 and HDAC4. The most selective compound resulted 5a, with a SI of 11.9. The enzymatic inhibitory activity of these conjugated compounds was relatively weak; however, some of these compounds showed significant effect in inducing apoptosis. Moreover, the anti-proliferative activity in cancer cells resulted quite promising, especially in the HCT119 cell line.
Su
Hong
H
Department of Medicinal Chemistry, China Pharmaceutical University, People's Republic of China.
Nebbioso
Angela
A
Carafa
Vincenzo
V
Chen
Yadong
Y
Yang
Bo
B
Altucci
Lucia
L
You
Qidong
Q
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001665:Binding Sites; D015153:Blotting, Western; D002453:Cell Cycle / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000096:biosynthesis / Q000187:drug effects; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D004789:Enzyme Activation / Q000187:drug effects; D056284:Histone Deacetylase 1; D006655:Histone Deacetylases / Q000737:chemistry / Q000187:drug effects*; D006801:Humans; D006877:Hydroxamic Acids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D008024:Ligands; D015394:Molecular Structure; D011994:Recombinant Proteins / Q000187:drug effects; D012097:Repressor Proteins / Q000737:chemistry / Q000187:drug effects*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013997:Time Factors; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D050759:Cyclin-Dependent Kinase Inhibitor p21; D006877:Hydroxamic Acids; D008024:Ligands; D011994:Recombinant Proteins; D012097:Repressor Proteins; C110550:HDAC1 protein, human; C400300:HDAC4 protein, human; D056284:Histone Deacetylase 1; D006655:Histone Deacetylases