Targets and patented drugs for chemotherapy of Chagas disease

Chagas diseaseis a parasitic infection typically spread by triatomine vectors, affecting millions of people all over Latin America. Existing chemotherapy is centered on benznidazole and nifurtimox, providing unsatisfactory results and substantial side effects. The transmission of the disease by people migration has determined the emergence as a public health problem elsewhere in non-endemic countries of the word.So, the finding of novel ways to challenge this neglected disease is a main priority. Progress in scientific knowledge about Trypanosoma cruzi in the period comprising last 15-years has increased the identification of multiple targets for Chagas´ disease chemotherapy. Ergosterol biosynthesis pathway and cruzipain, the key cysteine protease (CP) of T.cruzi, considered as the best encouraging targets for trypanocidal drugs. Recent unfortunate clinical trials investigating the administration of pozoconazole and ravuconazole to chronic patients; an approach for the fast development of novel anti-T.cruzi chemotherapy focused on the CP inhibitor K777, which is close to entering the clinical trial phase. The combination of known drugs with existing trypanocidal agents and compounds recently identified as clinical candidates for Chagas disease can be considered among the finest points of the manuscript. In addition, trypanothione biosynthesis, thiol-dependant redox and polyamine metabolism, the glycolytic, glyconeogenic, pentose phosphate, lipidic and polyisoprenoid biosynthetic pathways, and specific enzymes from these biosynthetic pathways have been also specifically discussed. Novel synthesized anti-T. cruzi compounds with or without specific single or multi-target assigned have been also described in detail. In summary, loans on anti-Chagas disease agents focused to specific parasite targets as their metabolic pathways or specific enzymes have been summarized. Patent literature collected and published from 2000 to 2015, alleging inhibitors for specific T. cruzi targets or trypanocidal activity was achieved over the search database from Delphion Research intellectual property network including international patents and the European patent office, Espacenet.

###

For more information about the article, please visit https://benthamscience.com/journals/recent-patents-on-anti-infective-drug-discovery/volume/11/issue/2/page/74/

Reference: Duschak, VG.; (2016). Targets and Patented Drugs for Chemotherapy of Chagas Disease in the Last 15 Years-Period. Recent Patents on Anticancer Drug Discovery, DOI: 10.2174/1574891X11666161024165304