Journal of Medicinal Chemistry p. 8389 - 8403 (2013)
Update date:2022-08-15
Topics:
Nitsche, Christoph
Schreier, Verena N.
Behnam, Mira A. M.
Kumar, Anil
Bartenschlager, Ralf
Klein, Christian D.
The protease of dengue virus is a promising target for antiviral drug discovery. We here report a new generation of peptide-hybrid inhibitors of dengue protease that incorporate N-substituted 5-arylidenethiazolidinone heterocycles (rhodanines and thiazolidinediones) as N-terminal capping groups of the peptide moiety. The compounds were extensively characterized with respect to inhibition of various proteases, inhibition mechanisms, membrane permeability, antiviral activity, and cytotoxicity in cell culture. A sulfur/oxygen exchange in position 2 of the capping heterocycle (thiazolidinedione-capped vs rhodanine-capped peptide hybrids) has a significant effect on these properties and activities. The most promising in vitro affinities were observed for thiazolidinedione-based peptide hybrids containing hydrophobic groups with Ki values between 1.5 and 1.8 μM and competitive inhibition mechanisms. Rhodanine-capped peptide hybrids with hydrophobic substituents have, in correlation with their membrane permeability, a more pronounced antiviral activity in cell culture than the thiazolidinediones.
View MoreZhejiang Sanmei Chemical Industry Co., Ltd
Contact:86-579-87633213
Address:Huchu Industrial Zone, Qingnian Rd., Wuyi County, Zhejiang Prov., China.
Contact:
Address:
Shandong Xinke Petrochemical Co., Ltd.
Contact:+86-546-7277016
Address:Gudao Industrial Park, Hekou District, Dongying, Shandong Province, China
Contact:15973022782
Address:7-5-6218,Incubation Centre,Guandong Industry Park, East Lake High-Tech Development Zone,Wuhan City.
Daqing New Century Fine Chemical Co., Ltd.
Contact:010-57126694
Address:No.39, jinxing cun, honggang district
Doi:10.1021/ml200093v
(2011)Doi:10.1002/chem.201201325
(2012)Doi:10.1007/s00044-012-0244-2
(2013)Doi:10.1002/anie.201203507
(2012)Doi:10.1002/anie.201203914
(2012)Doi:10.1021/acsmedchemlett.8b00596
(2019)