Produção Nacional
Revisado por pares
SAR of a series of anti-HSV-1 acridone derivatives, and a rational acridone-based design of a new anti-HSV-1 3H-benzo[b]pyrazolo[3,4-h]-1,6-naphthyridine series
2007; Elsevier BV; Volume: 16; Issue: 1 Linguagem: Inglês
10.1016/j.bmc.2007.09.032
ISSN1464-3391
AutoresAlice M. R. Bernardino, Helena Carla Castro, Izabel C.P.P. Frugulhetti, Natália I.V. Loureiro, A. Azevedo, Luiz C. S. Pinheiro, Thiago Moreno L. Souza, Viveca Giongo, Fabiana Passamani, Uiaran O. Magalhães, Magaly Girão Albuquerque, Lourdes Maria Corrêa Cabral, Carlos Rangel Rodrigues,
Tópico(s)Drug-Induced Adverse Reactions
ResumoHerpes Simplex Virus (HSV) infections are among the most common human diseases. In this work, we assess the structural features and electronic properties of a series of ten 1-hydroxyacridone derivatives (1a–j) recently described as a new class of non-nucleoside inhibitors of Herpes Simplex Virus-1 (HSV-1). Based on these molecules, we applied rigid analogue and isosteric replacement approaches to design and synthesize nine new 3H-benzo[b]pyrazolo[3,4-h]-1,6-naphthyridine derivatives (2a–i). The biological and computational results of these new molecules were compared with 1-hydroxyacridones. An inhibitory profile was observed in 10-Cl substituted 3H-benzo[b]pyrazolo[3,4-h]-1,6-naphthyridine derivative (2f), which presents the same substituent at the analogous position of 1-hydroxyacridone derivative (1b). The structure–activity relationship (SAR) studies pointed out the 10-position next to nitrogen atom as important for the anti-HSV-1 profile in the pyrazolo-naphthyridine derivatives tested, which reinforced the promising profile for further experimental investigation. The most potent acridone and pyrazolo-naphthridine derivatives were also submitted to an in silico ADMET screening in order to determine their overall drug-score, which confirmed their potential antiviral profile.
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