Discovery of Novel Inhibitors of Cruzain Cysteine Protease of Trypanosoma cruzi


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Abstract

Chagas disease (CD) is a parasitic disease endemic in several developing coun-tries. According to the World Health Organization, approximately 6-8 million people worldwide are inflicted by CD. The scarcity of new drugs, mainly for the chronic phase, is the main reason for treatment limitation in CD. Therefore, there is an urgent need to dis-cover new targets for which new therapeutical agents could be developed. Cruzain cyste-ine protease (CCP) is a promising alternative because this enzyme exhibits pleiotropic ef-fects by acting as a virulence factor, modulating host immune cells, and interacting with host cells. This systematic review was conducted to discover new compounds that act as cruzain inhibitors, and their effects in vitro were studied through enzymatic assays and molecular docking. Additionally, the advances and perspectives of these inhibitors are discussed. These findings are expected to contribute to medicinal chemistry in view of the design of new, safe, and efficacious inhibitors against Trypanosoma cruzi CCP detected in the last decade (2013-2022) to provide scaffolds for further optimization, aiming toward the discovery of new drugs.

About the authors

João Prates

Department of Drugs and Medicine, School of Pharmaceutical Sciences,, São Paulo State University (UNESP)

Email: info@benthamscience.net

Juliana Lopes

Department of Drugs and Medicine, School of Pharmaceutical Sciences,, São Paulo State University (UNESP),

Email: info@benthamscience.net

Chung Chin

Department of Drugs and Medicine, School of Pharmaceutical Sciences, São Paulo State University (UNESP)

Email: info@benthamscience.net

Elizabeth Ferreira

LAPEN-Laboratory of Design and Synthesis of Chemotherapeutic Agents Potentially Active on Neglected Diseases, Department of Pharmacy, School of Pharmaceutical Sciences,, University of São Paulo (USP),

Email: info@benthamscience.net

Jean dos Santos

Department of Drugs and Medicine, School of Pharmaceutical Sciences,, São Paulo State University (UNESP)

Email: info@benthamscience.net

Cauê Scarim

Department of Drugs and Medicine, School of Pharmaceutical Sciences,, São Paulo State University (UNESP),

Author for correspondence.
Email: info@benthamscience.net

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