Abstract:
Lavendamycin, an anti-tumor antibiotic isolated from the bacterial species Streptomyces lavendulae in 1981, proved to possess limited applicability due to high toxicity and difficulty in synthesizing large quantities in earlier studies. In 1993, a highly efficient procedure for the synthesis of lavendamycin analogs was discovered in the chemistry department at Ball State University. In this study, a number of these analogs have been assayed for their anti-retroviral potential alone and for their potential use in combined drug therapy.In this study, we assayed the anti-retroviral activity of twenty lavendamycin analogs in vitro via comparison to a known anti-retroviral agent, streptonigrin. In addition, we assessed the anti-retroviral potential of combination therapy of lavendamycin analogs combined with zidovudine (AZT-TP). We found the twenty lavendamycin analogs to induce a dose-dependent inhibition on HIV-1 reverse transcriptase, with eight analogs at 30 uM inhibiting reverse transcriptase activity more than fifty percent, all eight of which possessed higher anti-HIV-RT activity than streptonigrin. Analysis of the combination of lavendamycin analogs with AZT-TP showed possible synergistic activity for all analogs assayed, particularly at lower concentrations. The anti-retroviral activity of lavendamycin analogs combined with AZT-TP varied considerably between the lavendamycin analogs assayed, ranging from antagonistic to synergistic effects depending on the dose of both the lavendamycin analog and AZT-TP.