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Bioorg Med Chem Lett ; 40: 127926, 2021 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-33705902

RESUMO

This work presents the design and synthesis of camphor, fenchone, and norcamphor N-acylhydrazone derivatives as a new class of inhibitors of the Hantaan virus, which causes haemorrhagic fever with renal syndrome (HFRS). A cytopathic model was developed for testing chemotherapeutics against the Hantaan virus, strain 76-118. In addition, a study of the antiviral activity was carried out using a pseudoviral system. It was found that the hit compound possesses significant activity (IC50 = 7.6 ± 2 µM) along with low toxicity (CC50 > 1000 µM). Using molecular docking procedures, the binding with Hantavirus nucleoprotein was evaluated and the correlation between the structure of the synthesised compounds and the antiviral activity was established.


Assuntos
Antivirais/farmacologia , Canfanos/farmacologia , Vírus Hantaan/efeitos dos fármacos , Hidrazonas/farmacologia , Isoindóis/farmacologia , Norbornanos/farmacologia , Animais , Antivirais/síntese química , Antivirais/metabolismo , Canfanos/síntese química , Canfanos/metabolismo , Proteínas do Capsídeo/metabolismo , Cães , Desenho de Fármacos , Células HEK293 , Humanos , Hidrazonas/síntese química , Hidrazonas/metabolismo , Isoindóis/síntese química , Isoindóis/metabolismo , Células Madin Darby de Rim Canino , Testes de Sensibilidade Microbiana , Simulação de Acoplamento Molecular , Norbornanos/síntese química , Norbornanos/metabolismo , Ligação Proteica , Proteínas do Core Viral/metabolismo
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