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Letters in Drug Design & Discovery

Author(s): Caroline Reis Santiago Paschoal, Vitor Won-Held Rabelo, Tamillis Figueiredo de Oliveira and Paula Alvarez Abreu*

DOI: 10.2174/1570180820666230816141241

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Exploring Brazilian Natural Products as Potential Bioactive Compounds against Trypanosoma cruzi by Targeting Squalene Synthase

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Abstract

Introduction: Chagas disease is a neglected disease caused by the protozoan Trypanosoma cruzi that affects 7 million people worldwide. The current treatment is limited due to safety and efficacy issues. Therefore, the search for new antiparasitic drugs is fundamental. The enzyme squalene synthase (SQS) is an attractive therapeutic target since it participates in the ergosterol biosynthesis pathway.

Objective: In the present study, we explored the Brazilian biodiversity to search for potential inhibitors of T. cruzi SQS (TcSQS) using ligand and structure-based virtual screening strategies.

Materials and Methods: A virtual screening was performed within the NuBBE database, with more than 2,200 natural products (NP) or semisynthetic derivatives from the Brazilian biodiversity. Molecular docking and ADMET predictions were then performed.

Results: A set of 12 NP showed interactions with TcSQS like those observed by known inhibitors and shared literature evidence that supports the predicted activity.

Conclusion: Three compounds (flavonoids) showed good ADMET properties as potential inhibitors of TcSQS.

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