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Arg-substituted VmCT1 analogs reveals promising candidate for the development of new antichagasic agent

Published online by Cambridge University Press:  02 October 2020

Cibele Nicolaski Pedron ,
Katielle Albuquerque Freire ,
Marcelo Der Torossian Torres ,
Dânya Bandeira Lima ,
Marília Lopes Monteiro ,
Ramon Róseo Paula Pessoa Bezerra de Menezes ,
Alice Maria Costa Martins Open the ORCID record for Alice Maria Costa Martins [Opens in a new window]  and
Vani Xavier Oliveira Junior Open the ORCID record for Vani Xavier Oliveira Junior [Opens in a new window]
Cibele Nicolaski Pedron
Affiliation:
Centro de Ciências Naturais e Humanas, Universidade Federal do ABC, Santo André, 09210580, SP, Brazil Departamento de Biofísica, Universidade Federal de São Paulo, São Paulo, 04044020, SP, Brazil
Katielle Albuquerque Freire
Affiliation:
Centro de Ciências Naturais e Humanas, Universidade Federal do ABC, Santo André, 09210580, SP, Brazil
Marcelo Der Torossian Torres
Affiliation:
Centro de Ciências Naturais e Humanas, Universidade Federal do ABC, Santo André, 09210580, SP, Brazil
Dânya Bandeira Lima
Affiliation:
Departamento de Análises Clínicas e Toxicológicas, Faculdade de Farmácia, Universidade Federal do Ceará, Fortaleza, 60430372, CE, Brazil
Marília Lopes Monteiro
Affiliation:
Departamento de Análises Clínicas e Toxicológicas, Faculdade de Farmácia, Universidade Federal do Ceará, Fortaleza, 60430372, CE, Brazil
Ramon Róseo Paula Pessoa Bezerra de Menezes
Affiliation:
Departamento de Análises Clínicas e Toxicológicas, Faculdade de Farmácia, Universidade Federal do Ceará, Fortaleza, 60430372, CE, Brazil
Alice Maria Costa Martins
Affiliation:
Departamento de Análises Clínicas e Toxicológicas, Faculdade de Farmácia, Universidade Federal do Ceará, Fortaleza, 60430372, CE, Brazil
Vani Xavier Oliveira Junior*
Affiliation:
Centro de Ciências Naturais e Humanas, Universidade Federal do ABC, Santo André, 09210580, SP, Brazil Departamento de Biofísica, Universidade Federal de São Paulo, São Paulo, 04044020, SP, Brazil
*
Author for correspondence: Vani Xavier de Oliveira Junior, E-mail: vani.junior@ufabc.edu.br
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Abstract

VmCT1 is an antimicrobial peptide (AMP) isolated from the venom of the scorpion Vaejovis mexicanus with antimicrobial, anticancer and antimalarial activities, which the rational design with Arg-substitution has yielded AMPs with higher antimicrobial activity than VmCT1. Chagas is a neglected tropical disease, becoming the development of new antichagasic agents is urgent. Thus, we aimed to evaluate the antichagasic effect of VmCT1 and three Arg-substituted analogues, as well their action mechanism. Peptides were tested against the epimastigote, trypomastigote, amastigote forms of Trypanossoma cruzi Y strain and against LLC-MK2 mammalian cells. The mechanism of action of these peptides was evaluated by means of flow cytometry and scanning electron microscopy. VmCT1 presented activity against all three forms of T. cruzi, with EC50 against trypomastigote forms of 1.37 μmol L−1 and selectivity index (SI) of 58. [Arg]3-VmCT1, [Arg]7-VmCT1 and [Arg]11-VmCT1 also showed trypanocidal effect, but [Arg]11-VmCT1 had the best effect, being able to decrease the EC50 against trypomastigote forms to 0.8 μmol L−1 and increase SI to 175. Necrosis was cell death pathway of VmCT1, as well [Arg]7-VmCT1 and [Arg]11-VmCT1, such as observed by membrane damage in flow cytometry analyses and scanning-electron-microscopy. In conclusion, [Arg]11-VmCT1 revealed promising as a candidate for new antichagasic therapeutics.

Keywords

Antimicrobial peptidesChagas diseasescorpion venom peptideTrypanosoma cruziVmCT1
Type
Research Article
Information
Parasitology , Volume 147 , Issue 14 , December 2020 , pp. 1810 - 1818
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Copyright
Copyright © The Author(s) 2020. Published by Cambridge University Press

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Footnotes

*

Present address: Machine Biology Group, Departments of Psychiatry and Microbiology, Institute for Biomedical Informatics, Institute for Translational Medicine and Therapeutics, Perelman School of Medicine, and Department of Bioengineering, University of Pennsylvania, Philadelphia, 19104, PA, USA.

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