Planning new Trypanosoma cruzi CYP51 inhibitors using QSAR studies

Chagas disease kills over 10,000 people per year, and approximately 8 million people are infected by Trypanosoma cruzi . The reference drug for treatment of the disease, benznidazole, is the same since the 70s. In recent years, many CYP51 inhibitors were tested against this parasite’s target. One of...

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Bibliographic Details
Published in:	Molecular diversity Vol. 25; no. 4; pp. 2219 - 2235
Main Authors:	de Oliveira, Pedro Igor Camara, de Santana Miranda, Paulo Henrique, Lourenço, Estela Mariana Guimaraes, de Santana Nogueira Silverio, Priscilla Suene, Barbosa, Euzebio Guimaraes
Format:	Journal Article
Language:	English
Published:	Cham Springer International Publishing 01-11-2021 Springer Nature B.V
Subjects:	14-alpha Demethylase Inhibitors - chemical synthesis 14-alpha Demethylase Inhibitors - chemistry 14-alpha Demethylase Inhibitors - pharmacology Biochemistry Biomedical and Life Sciences Chagas Disease - drug therapy Cytochrome P-450 Enzyme System Humans Life Sciences Models, Molecular Organic Chemistry Original Article Pharmacy Polymer Sciences Protozoa Quantitative Structure-Activity Relationship Sterol 14-Demethylase - chemistry Sterol 14-Demethylase - metabolism Trypanocidal Agents - chemical synthesis Trypanocidal Agents - chemistry Trypanocidal Agents - pharmacology Trypanosoma cruzi - drug effects Trypanosoma cruzi - enzymology Chagas disease Structure-based drug design QSAR CYP51 Trypanosoma cruzi
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Summary:	Chagas disease kills over 10,000 people per year, and approximately 8 million people are infected by Trypanosoma cruzi . The reference drug for treatment of the disease, benznidazole, is the same since the 70s. In recent years, many CYP51 inhibitors were tested against this parasite’s target. One of them, posaconazole, was even tested in clinical trials that unfortunately were not successful. Nevertheless, there are still many evidences that CYP51 is a great potential target to treat T. cruzi infection. The research for new effective molecules that can cure the chronic phase of the disease is essential. 2D and 3D-quantitative structure activity relationship (QSAR) studies were conducted in this work to create three QSAR models using the chemical structures of 197 published compounds that already went through either in vivo or in vitro tests. After the analysis of the models, new analogues not yet synthesized were suggested here and had their biological activity and synthetic availability assessed. Graphic abstract
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1381-1991 1573-501X 1573-501X
DOI:	10.1007/s11030-020-10113-2