Chagas Disease: Perspectives on the Past and Present and Challenges in Drug Discovery
Felipe Raposo Passos Mansoldo,
Fabrizio Carta,
Andrea Angeli,
Veronica da Silva Cardoso,
Claudiu T. Supuran,
Alane Beatriz Vermelho
Affiliations
Felipe Raposo Passos Mansoldo
BIOINOVAR-Biocatalysis, Bioproducts and Bioenergy, Institute of Microbiology Paulo de Góes, Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro 21941-902, Brazil
Fabrizio Carta
Neurofarba Department, Università degli Studi di Firenze, Sezione di Scienze Farmaceutiche, Via Ugo Schiff 6, 50019 Sesto Fiorentino (Florence), Italy
Andrea Angeli
Neurofarba Department, Università degli Studi di Firenze, Sezione di Scienze Farmaceutiche, Via Ugo Schiff 6, 50019 Sesto Fiorentino (Florence), Italy
Veronica da Silva Cardoso
BIOINOVAR-Biocatalysis, Bioproducts and Bioenergy, Institute of Microbiology Paulo de Góes, Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro 21941-902, Brazil
Claudiu T. Supuran
Neurofarba Department, Università degli Studi di Firenze, Sezione di Scienze Farmaceutiche, Via Ugo Schiff 6, 50019 Sesto Fiorentino (Florence), Italy
Alane Beatriz Vermelho
BIOINOVAR-Biocatalysis, Bioproducts and Bioenergy, Institute of Microbiology Paulo de Góes, Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro 21941-902, Brazil
Chagas disease still has no effective treatment option for all of its phases despite being discovered more than 100 years ago. The development of commercial drugs has been stagnating since the 1960s, a fact that sheds light on the question of how drug discovery research has progressed and taken advantage of technological advances. Could it be that technological advances have not yet been sufficient to resolve this issue or is there a lack of protocol, validation and standardization of the data generated by different research teams? This work presents an overview of commercial drugs and those that have been evaluated in studies and clinical trials so far. A brief review is made of recent target-based and phenotypic studies based on the search for molecules with anti-Trypanosoma cruzi action. It also discusses how proteochemometric (PCM) modeling and microcrystal electron diffraction (MicroED) can help in the case of the lack of a 3D protein structure; more specifically, Trypanosoma cruzi carbonic anhydrase.
