| Abstract
| - We have recently discovered that 6-aminoquinolone derivatives could be valid leads for thedevelopment of new anti-HIV agents because of their new and diversified mode of action. Infact, studies carried out on the lead WM5 showed that this derivative is able to inhibit theTat-mediated long terminal repeat driven transcription, an essential step in the HIV-1replication cycle. Thus, starting from lead WM5, we performed the design and synthesis of anenlarged series of 6-aminoquinolones, which permitted some very potent anti-HIV 6-aminoderivatives to be obtained and the structure−activity relationship to be delineated. Somederivatives, 26c, 26e, 26i, and 26j, proved to be highly effective in inhibiting HIV replicationat 50% inhibitory concentration in the range of 0.0087−0.7 μg/mL in MT-4, PBMCs and CEMcell lines coupled with positive selectivity indexes that reach values higher than 1000 on CEMcell lines for compounds 26e and 26i. Time-of-addition experiments clearly confirm that thenew, potent 6-aminoquinolones interact at a postintegration step in the replication cycle ofHIV.
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