Lavendamycin, an aminoquinolinedione antibiotic is similar to streptonigrin, an antibiotic with known antiretroviral activity. Their applicability as drugs is limited due to their high toxicity to mammalian cells. A series of novel analogs of lavendamycin has been recently synthesized. In initial screening, three of the analogs showed significant inhibitory activity toward the reverse transcriptase (RT) of the avian myeloblastosis virus (AMV) and exhibited little or no animal toxicity and relatively low cellular cytotoxicity.In this study, we determined the anti-retroviral activity of nine analogs by assessing their anti-reverse transcriptase(anti-RT) activity in comparison to streptonigrin. Using both the human immunodeficiency virus (HIV) and AMV reverse transcriptase in vitro we found that the analogs exhibited significant anti-RT activity. The inhibitory activity of the analogs was dose dependent, and they had different effects on the two enzymes. At 30 µM seven of the analogs inhibited HIV-RT activity by 50% or more. At this concentration, two of the analogs were significantly more effective than streptonigrin. AMV-RT was more sensitive toward both streptonigrin and several of the analogs than was HIV-RT. Furthermore, combination of azidothymidine (AZT)-triphosphate (TP) and several of analogs showed synergistic inhibitory effects at low doses. / Department of Biology