- Exploring naphthyl-carbohydrazides as inhibitors of influenza A viruses
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A library of hydrazide derivatives was synthesized to target non-structural protein 1 of influenza A virus (NS1) as a means to develop anti-influenza drug leads. The lead compound 3-hydroxy-N-[(Z)-1-(5,6,7,8-tetrahydronaphthalen-2-yl) ethylideneamino]naphthalene-2-carboxamide, which we denoted as "HENC", was identified by its ability to increase the melting temperature of the effector domain (ED) of the NS1 protein, as assayed using differential scanning fluorimetry. A library of HENC analogs was tested for inhibitory effect against influenza A virus replication in MDCK cells. A systematic diversification of HENC revealed the identity of the R group attached to the imine carbon atom significantly influenced the antiviral activity. A phenyl or cyclohexyl at this position yielded the most potent antiviral activity. The phenyl containing compound had antiviral activity similar to that of the active form of oseltamivir (Tamiflu), and had no detectable effect on cell viability.
- Barman, Sanmitra,You, Lei,Chen, Ran,Codrea, Vlad,Kago, Grace,Edupuganti, Ramakrishna,Robertus, Jon,Krug, Robert M.,Anslyn, Eric V.
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- Study of E/Z isomerization in a series of novel non-ligand binding pocket androgen receptor antagonists
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We report the conformational analysis of a series of 3-hydroxy-N′- ((naphthalen-2-yl)methylene)naphthalene-2-carbohydrazides. This class of compounds has recently been reported as androgen receptor (AR)-coactivator disruptors for potential application in prostate cancer therapy. Definition of the E/Z isomerism around the imine linker group (hydrazide) is significant from a mechanistic point of view. A detailed study using theoretical calculations coupled with experimental techniques has allowed us determine an initial preference for the E isomer. The biological activity of newly synthesized compounds at the androgen receptor, along with a series of structural analogs, was determined and provides the basis for preliminary qualitative structure-activity relationship analysis.
- Blanco, Fernando,Caboni, Laura,Fayne, Darren,Lloyd, David G.,Egan, Billy,Meegan, Mary J.,O'Brien, John,McCabe, Thomas,Elguero, Jose
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p. 2387 - 2397,11
(2020/08/24)
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