Novel cruzipain inhibitors for the chemotherapy of chronic Chagas disease

SBARAGLINI ML; BELLERA CL; FRACCAROLI L; LAROCCA L; CARRILLO C; TALEVI A; ALBA SOTO CD

INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS

ELSEVIER SCIENCE BV

Lugar: Amsterdam; Año: 2016 vol. 2016 p. 1 - 10

0924-8579

In spite of current efforts worldwide to develop new medications against Chagas disease, only two drugs are available, nifurtimox and benznidazole. Both drugs require prolonged treatment, have multiple side effects and limited efficacy on adult patients chronically infected with Trypanosoma cruzi. Recently, computer-guided drug repositioning led to discovery of the trypanocidal effects of clofazimine and benidipine. These compounds showed inhibitory effects on cruzipain, the major cysteine protease of the parasite, on different T. cruzi stages and in a mouse model of acute Chagas disease. The aim of this work was to test the efficacy of these novel cruzipain inhibitors when administered to a model of chronic Chagas disease. Benidipine and clofazimine were able to reduce the parasite burden in cardiac and skeletal muscle of chronically infected mice compared to the untreated ones, and diminished the inflammatory process on these tissues. Further studies should be performed to study the synergism with benznidazole and nifurtimox in view of combined therapies.