Synthesis and biological evaluation of 1-arylsulfonyl-5-(N-hydroxyacrylamide)indoles as potent histone deacetylase inhibitors with antitumor activity in vivo.

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Lai MJ, Huang HL, Pan SL, Liu YM, Peng CY, Lee HY, Yeh TK, Huang PH, Teng CM, Chen CS, Chuang HY, Liou JP

Synthesis and biological evaluation of 1-arylsulfonyl-5-(N-hydroxyacrylamide)indoles as potent histone deacetylase inhibitors with antitumor activity in vivo.

J Med Chem. 2012 Apr 26;55(8):3777-91. doi: 10.1021/jm300197a. Epub 2012 Apr 5.

PubMed ID
22439863 [ View in PubMed
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Abstract

A series of 1-arylsulfonyl-5-(N-hydroxyacrylamide)indoles has been identified as a new class of histone deacetylase inhibitors. Compounds 8, 11, 12, 13, and 14 demonstrated stronger antiproliferative activities than 1 (SAHA) with GI(50) values ranging from 0.36 to 1.21 muM against Hep3B, MDA-MB-231, PC-3, and A549 human cancer cell lines. Lead compound 8 showed remarkable HDAC 1, 2, and 6 isoenzymes inhibitory activities with IC(50) values of 12.3, 4.0, 1.0 nM, respectively, which are comparable to 1. In in vivo efficacy evaluation against lung A549 xenograft model, 8 displayed better antitumor activity than compound 1.

DrugBank Data that Cites this Article

Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
VorinostatHistone deacetylase 1IC 50 (nM)8.9N/AN/ADetails
VorinostatHistone deacetylase 2IC 50 (nM)1.7N/AN/ADetails
VorinostatHistone deacetylase 6IC 50 (nM)5N/AN/ADetails