Novel cruzipain inhibitors for the chemotherapy of chronic Chagas disease

MARÍA L. SBARAGLINI; CAROLINA L. BELLERA; LAURA FRACCAROLI; LUCIANA LAROCCA; CAROLINA CARRILLO; ALAN TALEVI; CATALINA ALBA SOTO

INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS

ELSEVIER SCIENCE BV

Lugar: Amsterdam; Año: 2016 vol. 48 p. 91 - 95

0924-8579

In spite of the efforts all over de worldcurrent efforts worldwide to develop new medications to treat Chagas disease, only two drugs are available for the treatment of Chagas disease, Nifurtimox and Benznidazole, and both require extensive treatments with severe toxicity and have controversial efficacy in Trypanosoma. cruzi-infected adults with chronic status. Bellera CL et al.Recently, has previously applied computer-guided drug repositioning led to the discovery of the trypanocidal effects for the search of novel Cruzipain inhibitorof clofazimine and benidipine, the major cystein protease of the parasite. The inhibitory effect of this These compounds, benidipine and clofazimine, shown inhibitory effects on was confirmed in cruzipain, the major cysteine protease of the parasite, enzymatic assays, against different T. cruzi stages and in a mouse model of acute Chagas diseaseinfection. The aim of this work was to test the efficacy of these novel cruzipain inhibitors in a model of chronic Chagas disease infection, finding a direct effect on parasite elimination at the chronic stage. Moreover, they were able Benidipine was able to reduce the parasite burden in blood and skeletal tissue of chronic chagasic mice treated compared with the untreated ones, while both compounds and diminished the pro-inflammatory effects of the pathology. Further studies should be performed, including synergism studies with benznidazole and nifurtimox.