New antibacterials for the treatment of toxoplasmosis; a patent review

RODRIGUEZ, JUAN BAUTISTA; SZAJNMAN, SERGIO HERNÁN

EXPERT OPINION ON THERAPEUTIC PATENTS

INFORMA HEALTHCARE

Año: 2012 vol. 22 p. 311 - 333

1354-3776

Introduction: Toxoplasmosma gondii is an opportunistic protozoan parasite, phylum Apicomplexa,  responsible for toxoplasmosis. T. gondii is able to infect a wide range of hosts, particularly humans and warm-blooded animals. Toxoplasmosis can be considered as one of the most prevalent parasitic diseases affecting close to one billion people worldwide. Particularly, this parasite can cause mortality among immunocompromised individuals such as AIDS patients, organ transplant as well as congenital infected children. Toxoplasmosis may lead to severe central nervous system disease. The current chemotherapy for the treatment of toxoplasmosis is still deficient. Areas covered: This review covers different approaches to toxoplasmosis chemotherapy focused on the metabolic differences of pharmacological relevance between the host and the parasite. Selective action on different targets such as the isoprenoid pathway (squalene synthase, farnesyl pyrophosphate synthase, D24(25)-sterol methyltransferase), dihydrofolate reductase, T. gondii adenosine kinase, and different antibacterials are discussed. Expert Opinion: The current chemotherapy to treat or prevent toxoplasmosis is still deficient based on the use of different drugs such as atovaquone, trimethoprim, spiramycine, etc. These compounds are only effective in acute phase of toxoplasmosis. These treatments are particularly disadvantageous in immunocompromised individuals because relapse of the disease may occur if the treatment is stopped. Certainly, a new and safe chemotherapy is need for this disease due to T. gondii causes serious morbidity and mortality in pregnant women and immunodeficient patients undergoing chemotherapy or people with AIDS. A particular drawback of the available treatments is the lack of efficacy against the tissue cyst of the parasite. The aim of this review was focused at presenting a broad scope of several attractive targets for rational design of drugs