Heme metabolism as a therapeutic target against protozoan parasites

Abstract

Neglected tropical diseases caused by protozoan parasites affect the life of millions of people worldwide, causing mortality, morbidity and high economic and social burden. The search for new drug targets and therapeutic strategies to fight these pathogens are necessary, since many current drugs have limited effects, cause severe side effects and their use has resulted in pathogen resistance. Heme (iron protoporphyrin IX) is a ubiquitous molecule important in many biological processes, including the homeostasis, growth and development of human pathogens such as trypanosomatids (Trypanosoma cruzi, Trypanosoma brucei and Leishmania spp.) and Plasmodium spp. In this review, several chemotherapy approaches and strategies are discussed that target heme transport, catabolism, crystallization and hemeproteins.

Keywords:

• Heme
• malaria
• trypanosomiasis
• leishmaniasis
• drugs
• neglected diseases
• photodynamic therapy
• heme-oxygenase

Acknowledgements

We would like to thank Dr. Norman A. Ratcliffe for his careful revision and relevant contribution for the manuscript. Molecular graphics were performed with the UCSF Chimera package. Chimera is a free software developed by the Resource for Biocomputing, Visualization, and Informatics at the University of California, San Francisco.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work was supported by research funds from the Oswaldo Cruz Institute of the Oswaldo Cruz Foundation (Fiocruz) and Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ). This work was finaced in part by the Coordenação de Aperfeiçoamento Pessoal de NÕvel Superior- Brasil (CAPES).