Infectious disease

Cell cultures and mouse studies identified multiple 7-deazaadenosine analogs that could help treat Chagas disease. Chemical synthesis and testing in human lung fibroblast cell-based assays of 7-deazaadenosine analogs yielded four compounds that inhibited growth of Trypanosoma cruzi with EC₅₀ values of 47-59 nM. In mice lethally infected with T. cruzi, two of the compounds given in 25 mg/kg oral doses twice daily for five days decreased circulating parasitemia by up to 99.8% compared with vehicle, with potency comparable to the anti-trypanosomal agent benznidazole. Also in the model, both compounds led to survival of all six treated animals up to 30 days post-treatment, whereas all six vehicle-treated animals died by day 15. Next steps could include optimizing the potency and PK of the compounds...