Abstract:
:Herpes 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.
journal_name
Bioorg Med Chemjournal_title
Bioorganic & medicinal chemistryauthors
Bernardino AM,Castro HC,Frugulhetti IC,Loureiro NI,Azevedo AR,Pinheiro LC,Souza TM,Giongo V,Passamani F,Magalhães UO,Albuquerque MG,Cabral LM,Rodrigues CRdoi
10.1016/j.bmc.2007.09.032subject
Has Abstractpub_date
2008-01-01 00:00:00pages
313-21issue
1eissn
0968-0896issn
1464-3391pii
S0968-0896(07)00818-8journal_volume
16pub_type
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