Abstract:
Lavendamycin is a naturally occurring antibiotic isolated from Streptomyces lavendulae. Like its related antibiotic, streptonigrin, lavendamycin has anti-tumor, antiviral and anti-bacterial activity and is highly toxic in its natural form. Several recently synthesized lavendamycin analogs were found to have low toxicity and significant activity against HIV-reverse transcriptase. Initial studies have shown at least a few of the novel analogs have considerable anti-HIV-RT activity alone and also synergistic effects when used in combination with AZT.In this study, four lavendamycin analogs were assessed in vitro for their optimum HIV-RT inhibitory ratios and concentrations with AZT. While most of the analogs showed additive and synergistic activity with AZT, MB 72 and MB 344 exhibited significant synergistic activity in combination with AZT. When tested with AZT at a constant ratio of 1:600, MB 344 was found to be the best candidate for drug therapy due to its very low toxicity, high inhibition of HIV-RT alone and with AZT and good solublility in water.
