The toxicity of adenosine analogues against Babesia bovis in vitro

The toxicities of 20 analogues of deoxyadenosine or adenosine were tested in vitro against the intraerythrocytic parasite Babesia bovis. IC37 values (the concentration of compound required to reduce cell survival to 37%) were determined for each compound. Tubercidin (7-deaza-adenosine), 2-bromo-adenosine, 8-bromo-3-ribosyl adenine and 6-phenylamino-deoxyadenosine were shown to be the most toxic towards B. bovis. Comparison of the toxicity results for these compounds in B. bovis with those in human melanoma cell lines indicated a differential toxicity, in that many of the compounds were toxic towards B. bovis but were relatively non-toxic towards human melanoma cell lines and vice versa. These results suggest that the mechanism of toxicity of the deoxyadenosine and adenosine analogues, whose normal metabolism involves transport, metabolism and incorporation into nucleic acids, may vary significantly between B. bovis and mammalian cells, allowing such drugs to be considered for parasite chemotherapy.