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Structural Investigation of the Naphthyridone Scaffold: Identification of a 1,6‐Naphthyridone Derivative with Potent and Selective Anti‐HIV Activity
Author(s) -
Tabarrini Oriana,
Massari Serena,
Sancineto Luca,
Daelemans Dirk,
Sabatini Stefano,
Manfroni Giuseppe,
Cecchetti Violetta,
Pannecouque Christophe
Publication year - 2011
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.201100073
Subject(s) - derivative (finance) , scaffold , chemistry , nucleus , human immunodeficiency virus (hiv) , selectivity , stereochemistry , combinatorial chemistry , identification (biology) , mechanism of action , computational biology , biology , biochemistry , microbiology and biotechnology , virology , in vitro , medicine , biomedical engineering , botany , financial economics , economics , catalysis
Building upon a large, previously reported series of anti‐HIV 6‐desfluoroquinolones endowed with a peculiar mechanism of action, the inhibition of Tat‐mediated transcription, replacement of the quinolone nucleus with a naphthyridone core was shown to be very productive. In this work, the naphthyridone scaffold was investigated in depth by synthesizing various analogues. This led to the identification of NM13 as the most selective derivative obtained in MT‐4 cells. It is the result of the successful combination of the 1,6‐naphthyridone nucleus and the C7 benzothiazolpiperazine group, which, for the first time, not only grants potent anti‐HIV activity but displays very high selectivity. Further studies aimed at a more thorough investigation of the anti‐HIV profile of this new derivative are in progress.