Two novel 6-desfluoroquinolone derivatives, HM-12 and HM-13, were evaluated for anti-human immunodeficiency virus (anti-HIV activity in acutely, chronically, and latently HIV type I (HIV-1)-infected cell cultures and were found to behave as potent HIV-1 transcription inhibitors. In order to extend this result in vivo, we developed an artificial hu-SCID mouse model for HIV-1 latency based on SCID mice engrafted with latently HIV-1-infected promyelocytic OM-10.1 cells in which HIV-1 can be reactivated in vivo by the administration of human tumor necrosis factor alpha (hTNF-alpha). Treating these SCID mice with HM-12 or HM-13 prior to hTNF-alpha stimulation resulted in a pronounced suppressive effect on viral reactivation. Since both quinolone derivatives were able to inhibit the reactivation of HIV-1 from this artificial viral reservoir in vivo, we provide encouraging evidence for the use of quinolones in the control of HIV-1 infections.
Stevens, M., Pollicita, M., Pannecouque, C., Verbeken, E., Tabarrini, O., Cecchetti, V., et al. (2007). Novel in vivo model for the study of human immunodeficiency virus type 1 transcription inhibitors: Evaluation of new 6-desfluoroquinolone derivatives. ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 51(4), 1407-1413 [10.1128/AAC.01251-06].
Novel in vivo model for the study of human immunodeficiency virus type 1 transcription inhibitors: Evaluation of new 6-desfluoroquinolone derivatives
POLLICITA, MICHELA;AQUARO, STEFANO;PERNO, CARLO FEDERICO;
2007-01-01
Abstract
Two novel 6-desfluoroquinolone derivatives, HM-12 and HM-13, were evaluated for anti-human immunodeficiency virus (anti-HIV activity in acutely, chronically, and latently HIV type I (HIV-1)-infected cell cultures and were found to behave as potent HIV-1 transcription inhibitors. In order to extend this result in vivo, we developed an artificial hu-SCID mouse model for HIV-1 latency based on SCID mice engrafted with latently HIV-1-infected promyelocytic OM-10.1 cells in which HIV-1 can be reactivated in vivo by the administration of human tumor necrosis factor alpha (hTNF-alpha). Treating these SCID mice with HM-12 or HM-13 prior to hTNF-alpha stimulation resulted in a pronounced suppressive effect on viral reactivation. Since both quinolone derivatives were able to inhibit the reactivation of HIV-1 from this artificial viral reservoir in vivo, we provide encouraging evidence for the use of quinolones in the control of HIV-1 infections.Questo articolo è pubblicato sotto una Licenza Licenza Creative Commons
