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1.
Bioorg Med Chem ; 23(24): 7777-84, 2015 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-26643220

RESUMO

We described the synthesis of a new congener series of 1,2,3-triazolyl-4-oxoquinolines and evaluated their ability to inhibit oseltamivir (OST)-resistant influenza strains. Oxoquinoline derivative 1i was the most potent compound within this series, inhibiting 94% of wild-type (WT) influenza neuraminidase (NA) activity. Compound 1i inhibited influenza virus replication with an EC50 of 0.2µM with less cytotoxicity than OST, and also inhibited different OST-resistant NAs. These results suggest that 1,2,3-triazolyl-4-oxoquinolines represent promising lead molecules for further anti-influenza drug design.


Assuntos
Antivirais/farmacologia , Vírus da Influenza A/efeitos dos fármacos , Vírus da Influenza B/efeitos dos fármacos , Influenza Humana/tratamento farmacológico , Oseltamivir/farmacologia , Quinolonas/farmacologia , Triazóis/farmacologia , Antivirais/química , Desenho de Fármacos , Farmacorresistência Viral , Humanos , Vírus da Influenza A/enzimologia , Vírus da Influenza B/enzimologia , Influenza Humana/virologia , Simulação de Acoplamento Molecular , Neuraminidase/antagonistas & inibidores , Neuraminidase/metabolismo , Quinolonas/química , Triazóis/química
2.
Curr Microbiol ; 62(5): 1349-54, 2011 May.
Artigo em Inglês | MEDLINE | ID: mdl-21225264

RESUMO

Herpes simplex virus is an important human pathogen responsible for a range of diseases from mild uncomplicated mucocutaneous infections to life-threatening ones. Currently, the emergence of Herpes simplex virus resistant strains increased the need for more effective and less cytotoxic drugs for Herpes treatment. In this work, we synthesized a series of oxoquinoline derivatives and experimentally evaluated the antiviral activity against acyclovir resistant HSV-1 strain as well as their cytotoxity profile. The most active compound (3b), named here as Fluoroxaq-3b, showed a promising profile with a better cytotoxicity profile than acyclovir. The theoretical analysis of the structure-activity relationship of these compounds revealed some stereoelectronic properties such as lower LUMO energy and lipophilicity, besides a higher polar surface area and number of hydrogen bond acceptor groups as important parameters for the antiviral activity. Fluoroxaq-3b showed a good oral theoretical bioavailability, according to Lipinski rule of five, with a promising profile for further in vivo analysis.


Assuntos
Antivirais/química , Antivirais/farmacologia , Herpes Simples/virologia , Herpesvirus Humano 1/efeitos dos fármacos , Quinolonas/química , Quinolonas/farmacologia , Animais , Antivirais/síntese química , Linhagem Celular , Chlorocebus aethiops , Herpes Simples/tratamento farmacológico , Humanos , Quinolonas/síntese química , Relação Estrutura-Atividade , Células Vero
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