Title: Structure modifications of 6-aminoquinolones with potent anti-HIV activity
Authors: Tabarrini, Oriana ×
Stevens, Miguel
Cecchetti, Violetta
Sabatini, Stefano
Dell'Uomo, Micaela
Manfroni, Giuseppe
Palumbo, Manlio
Pannecouque, Christophe
De Clercq, Erik
Fravolini, Arnaldo #
Issue Date: Oct-2004
Series Title: Journal of Medicinal Chemistry vol:47 issue:22 pages:5567-78
Abstract: We have recently discovered that 6-aminoquinolone derivatives could be valid leads for the development of new anti-HIV agents because of their new and diversified mode of action. In fact, studies carried out on the lead WM5 showed that this derivative is able to inhibit the Tat-mediated long terminal repeat driven transcription, an essential step in the HIV-1 replication cycle. Thus, starting from lead WM5, we performed the design and synthesis of an enlarged series of 6-aminoquinolones, which permitted some very potent anti-HIV 6-amino derivatives to be obtained and the structure-activity relationship to be delineated. Some derivatives, 26c, 26e, 26i, and 26j, proved to be highly effective in inhibiting HIV replication at 50% inhibitory concentration in the range of 0.0087-0.7 microg/mL in MT-4, PBMCs and CEM cell lines coupled with positive selectivity indexes that reach values higher than 1000 on CEM cell lines for compounds 26e and 26i. Time-of-addition experiments clearly confirm that the new, potent 6-aminoquinolones interact at a postintegration step in the replication cycle of HIV.
ISSN: 0022-2623
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory of Virology and Chemotherapy (Rega Institute)
Department of Microbiology & Immunology - miscellaneous
× corresponding author
# (joint) last author

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