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Design, Synthesis, and Docking Study of Acyl Thiourea Derivatives as Possible Histone Deacetylase Inhibitors with a Novel Zinc Binding Group
被引:13
作者:
Al-Amily, Duraid
[1
]
Mohammed, Mohammed H.
[1
]
机构:
[1] Univ Baghdad, Coll Pharm, Dept Pharmaceut Chem, Baghdad 10047, Iraq
关键词:
histone deacetylase inhibitors;
acyl thiourea derivatives;
zinc binding group;
distance from zinc ion;
MOLECULAR-MECHANISMS;
COMPLEXES;
DYNAMICS;
SYSTEM;
POTENT;
COPPER;
D O I:
10.3390/scipharm87040028
中图分类号:
R9 [药学];
学科分类号:
1007 ;
摘要:
Histone deacetylase inhibitors with zinc binding groups often exhibit drawbacks like non-selectivity or toxic effects. Thus, there are continuous efforts to modify the currently available inhibitors or to discover new derivatives to overcome these problems. One approach is to synthesize new compounds with novel zinc binding groups. The present study describes the utilization of acyl thiourea functionality, known to possess the ability to complex with metals, to be a novel zinc binding group incorporated into the designed histone deacetylase inhibitors. N-adipoyl monoanilide thiourea (4) and N-pimeloyl monoanilide thiourea (5) have been synthesized and characterized successfully. They showed inhibition of growth of human colon adenocarcinoma and mouse hepatoblastoma cells with low cytotoxic effect against normal human breast cells. Their binding mode to the active site of several histone deacetylases has been studied by docking and the results gave a preliminary indication that they could be successful histone deacetylase inhibitors.
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页数:15
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