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Δευτέρα 26 Οκτωβρίου 2020

A series of octahydroquinazoline-5-ones as novel inhibitors against dengue virus.

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A series of octahydroquinazoline-5-ones as novel inhibitors against dengue virus.

Eur J Med Chem. 2020 Aug 15;200:112318

Authors: Wan Y, Wu S, Zheng S, Liang E, Liu S, Yao X, Zhu Q

Abstract
A series of octahydroquinazoline-5-ones (OHQs 1-50) were designed and synthesized via an improved five-component reaction (5CR). Their bioactivities against dengue virus (DENV) were evaluated by determining lacate dehydrogenase (LDH) in the BHK-21 cells infected with DENV-2. Primary structure-activity relationship showed that six of OHQs with suitable substituents displayed good activities with EC50 = 1.31-1.85 μM. The primary bioactivity mechanism was investigated using the most potent OHQ 23. Experimental results indicate that 23 could efficiently reverse the DENV-2-induced cytopathic effect and suppress the expression of viral structure E protein, but showed no interaction with the MTase and RdRp domain of NS5, a protein plays an important role in viral genome transcription and viral protein translation. The efficient synthetic method, novel structures as DENV inhibitors and good activities are expected to be developed potential DENV inhibitors.

PMID: 32470709 [PubMed - indexed for MEDLINE]

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Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia@gmail.com,

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