Anti-Mycobacterium avium complex activities of streptcytosine analogs from a marine actinomycete as nucleoside antibiotics

To examine the potential of nucleoside antibiotics as therapeutic agents against Mycobacterium avium complex (MAC), the in vitro and in vivo anti-MAC activities of streptcytosine A (1), plicacetin (2), and bamicetin (3) derived from a marine actinomycete were evaluated. Compounds 1-3 exhibited antimicrobial activities against M. avium and M. intracellulare, with minimum inhibitory concentration values of 4.0 and 16 μg/mL, respectively, as assessed by the microdilution method. In silkworm infection models of M. avium and M. intracellulare, these compounds also exhibited therapeutic efficacies at lower doses than clarithromycin, with 50% effective doses of between 7.6 and 28 μg/larva·g, and no toxicity was observed. A pharmacokinetic analysis further revealed elimination half-lives of 3.0, 2.3, and 5.1 hours, respectively, in the silkworm hemolymph. These results suggest the potential of 1-3 as lead candidates for the development of potent anti-MAC drugs.