Author | Bermardino, Alice M. R. | |
Author | Azevedo, Alexandre R. | |
Author | Pinheiro, Luiz C. S. | |
Author | Borges, Júlio C. | |
Author | Paixão, Izabel C. P. | |
Author | Mesquita, Milene | |
Author | Souza, Thiago M. L. | |
Author | Santos, Maurício S. dos | |
Access date | 2017-05-11T15:05:18Z | |
Available date | 2017-05-11T15:05:18Z | |
Document date | 2012 | |
Citation | BERNARDINO, Alice M. R. et al. Synthesis and anti-HSV-1 evaluation of new 3H-benzo[b]pyrazolo[3,4-h]-1,6-naphthyridines and 3H-pyrido[2,3-b]pyrazolo[3,4-h]-1,6- naphthyridines. Organic and Medicinal Chemistry Letters, v.2:3, 7p, 2012. | pt_BR |
ISSN | 2191-2858 | pt_BR |
URI | https://www.arca.fiocruz.br/handle/icict/18820 | |
Language | eng | pt_BR |
Publisher | Springer Open | pt_BR |
Rights | open access | pt_BR |
Subject in Portuguese | Herpes simples | pt_BR |
Subject in Portuguese | Naftiridinas | pt_BR |
Title | Synthesis and anti-HSV-1 evaluation of new 3H-benzo[b]pyrazolo[3,4-h]-1,6-naphthyridines and 3H-pyrido[2,3-b]pyrazolo[3,4-h]-1,6- naphthyridines | pt_BR |
Type | Article | pt_BR |
Abstract | Background: Herpes simplex virus type-1 (HSV-1) is the primary cause of facial lesions (mouth, lips, and eyes) in
humans. The widespread use of acyclovir and nucleoside analogues has led to emergence of HSV strains that are
resistant to these drugs. Recently, non-nucleoside anti-HSV compounds have received considerable attention. 1,6-
Naphthyridines are a class of heterocyclic compounds that exhibit a broad spectrum of biological activities such as
inhibitor of HIV-1 integrase, HCMV, FGF receptor-1 tyrosine kinase, and the enzyme acetylcholinesterase. We
previously reported the synthesis, SAR studies, and evaluation anti-HSV-1 activity of 3H-benzo[b]pyrazolo[3,4-h]-1,6-
naphthyridines. In the course of our search for new 1,6-naphthyridines derivatives with potential activity against
HSV-1, we have synthesized and evaluated new 3H-benzo[b]pyrazolo[3,4-h]-1,6-naphthyridines (1a-k) and 3H-pyrido
[2,3-b]pyrazolo[3,4-h]-1,6-naphthyridines (2a-c).
Results: A known synthetic approach was used for preparing new 3H-benzo[b]pyrazolo[3,4-h]-1,6-naphthyridines
(1a-k) and 3H-pyrido[2,3-b]pyrazolo[3,4-h]-1,6-naphthyridines (2a-c), starting from ethyl 4-chloro-1-phenyl-1Hpyrazolo[
3,4-b]pyridine-5-carboxylate (7). All compounds were identified by FTIR, 1H NMR, and mass spectrometry.
The antiviral effect on HSV-1 virus replication was determined.
Conclusions: The compounds 1d, 1f, 1g, and 1h exhibited the highest anti-HSV-1 activity. In general, 3H-benzo[b]
pyrazolo[3,4-h]-1,6-naphthyridines were more effective inhibitors than their corresponding 3H-pyrido[2,3-b]pyrazolo
[3,4-h]-1,6-naphthyridines. The compound 1h reduced the virus yield in 91% at 50 μM and exhibited a low
cytotoxicity (CC50 600 μM). | pt_BR |
Affilliation | Universidade Federal Fluminense. Instituto de Química. Departamento de Química Orgânica. Programa de Pós-Graduação em Química. Niterói, RJ, Brasil. | pt_BR |
Affilliation | Universidade Federal Fluminense. Instituto de Química. Departamento de Química Orgânica. Programa de Pós-Graduação em Química. Niterói, RJ, Brasil. | pt_BR |
Affilliation | Universidade Federal Fluminense. Instituto de Química. Departamento de Química Orgânica. Programa de Pós-Graduação em Química. Niterói, RJ, Brasil. | pt_BR |
Affilliation | Universidade Federal Fluminense. Instituto de Química. Departamento de Química Orgânica. Programa de Pós-Graduação em Química. Niterói, RJ, Brasil. | pt_BR |
Affilliation | Universidade Federal Fluminense. Instituto de Biologia. Departamento de Biologia Celular e Molecular. Niterói, RJ, Brasil. | pt_BR |
Affilliation | Universidade Federal Fluminense. Instituto de Biologia. Departamento de Biologia Celular e Molecular. Niterói, RJ, Brasil / Fundação Oswaldo cruz. Instituto Oswaldo Cruz. Programa de Pós-Graduação em Biologia Celular e Molecular. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Universidade Federal Fluminense. Instituto de Biologia. Departamento de Biologia Celular e Molecular. Niterói, RJ, Brasil / Fundação Oswaldo cruz. Instituto Oswaldo Cruz. Programa de Pós-Graduação em Biologia Celular e Molecular. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Universidade Federal de Itajubá. Instituto de Ciências Exatas. Departamento de Física e Química. Itajubá, MG, Brasil. | pt_BR |
Subject | HSV-1 | pt_BR |
Subject | 1,6-naphthyridines | pt_BR |
Subject | pyrazolonaphthyridines | pt_BR |
Subject | heterocycles | pt_BR |