Guanidines Conjugated with Cell-Penetrating Peptides: A New Approach for the Development of Antileishmanial Molecules
Leishmaniasis is a neglected tropical disease caused by a protozoan of the genus Leishmania, which has visceral and cutaneous forms. The symptoms of leishmaniasis include high fever and weakness, and the cutaneous infection also causes lesions under the skin. The drugs used to treat leishmaniasis ha...
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2025-01-01
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| author | João Victor Marcelino de Souza Natalia C. S. Costa Maria C. O. Arruda Brasil Luana Ribeiro dos Anjos Renata Priscila Barros de Menezes Eduardo Henrique Zampieri Jhonatan Santos de Lima Angela Maria Arenas Velasquez Luciana Scotti Marcus Tullius Scotti Marcia A. S. Graminha Eduardo R. Pérez Gonzalez Eduardo Maffud Cilli |
| author_facet | João Victor Marcelino de Souza Natalia C. S. Costa Maria C. O. Arruda Brasil Luana Ribeiro dos Anjos Renata Priscila Barros de Menezes Eduardo Henrique Zampieri Jhonatan Santos de Lima Angela Maria Arenas Velasquez Luciana Scotti Marcus Tullius Scotti Marcia A. S. Graminha Eduardo R. Pérez Gonzalez Eduardo Maffud Cilli |
| author_sort | João Victor Marcelino de Souza |
| collection | DOAJ |
| description | Leishmaniasis is a neglected tropical disease caused by a protozoan of the genus Leishmania, which has visceral and cutaneous forms. The symptoms of leishmaniasis include high fever and weakness, and the cutaneous infection also causes lesions under the skin. The drugs used to treat leishmaniasis have become less effective due to the resistance mechanisms of the protozoa. In addition, the current compounds have low selectivity for the pathogen, leading to various side effects, which results in lower adherence to treatment. Various strategies were developed to solve this problem. The bioconjugation between natural compounds with antimicrobial activity and cell-penetrating peptides could alleviate the resistance and toxicity of current treatments. This work aims to conjugate the cell penetration peptide TAT to the guanidine GVL1. The GVL1-TAT bioconjugate exhibited leishmanicidal activity against <i>Leishmania amazonensis</i> and <i>Leishmania infantum</i> with a high selectivity index. In addition, the bioconjugate was more active against the intracellular enzyme CPP than the individual compounds. This target is very important for the viability and virulence of the parasite within the host cell. Docking studies confirmed the higher interaction of the conjugate with CPP and suggested that other proteins, such as trypanothione reductase, could be targeted. Thus, the data indicated that guanidines conjugated with cell-penetrating peptides could be a good approach for developing antileishmanial molecules. |
| format | Article |
| id | doaj-art-5f6eed6285b14fdb8ac7e9c920755f93 |
| institution | Kabale University |
| issn | 1420-3049 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj-art-5f6eed6285b14fdb8ac7e9c920755f932025-01-24T13:43:19ZengMDPI AGMolecules1420-30492025-01-0130226410.3390/molecules30020264Guanidines Conjugated with Cell-Penetrating Peptides: A New Approach for the Development of Antileishmanial MoleculesJoão Victor Marcelino de Souza0Natalia C. S. Costa1Maria C. O. Arruda Brasil2Luana Ribeiro dos Anjos3Renata Priscila Barros de Menezes4Eduardo Henrique Zampieri5Jhonatan Santos de Lima6Angela Maria Arenas Velasquez7Luciana Scotti8Marcus Tullius Scotti9Marcia A. S. Graminha10Eduardo R. Pérez Gonzalez11Eduardo Maffud Cilli12Department of Biochemistry and Organic Chemistry, Institute of Chemistry, São Paulo State University (UNESP), Araraquara 14800-060, SP, BrazilSchool of Pharmaceutical Sciences, São Paulo State University (UNESP), Araraquara 14800-903, SP, BrazilDepartment of Biochemistry and Organic Chemistry, Institute of Chemistry, São Paulo State University (UNESP), Araraquara 14800-060, SP, BrazilFine Organic Chemistry Lab, School of Sciences and Technology, São Paulo State University (UNESP), Presidente Prudente 19060-080, SP, BrazilNatural Products and Synthetic Bioactives Postgraduation Program, Federal Paraiba University (UFPB), João Pessoa 58051-900, PB, BrazilFine Organic Chemistry Lab, School of Sciences and Technology, São Paulo State University (UNESP), Presidente Prudente 19060-080, SP, BrazilSchool of Pharmaceutical Sciences, São Paulo State University (UNESP), Araraquara 14800-903, SP, BrazilSchool of Pharmaceutical Sciences, São Paulo State University (UNESP), Araraquara 14800-903, SP, BrazilNatural Products and Synthetic Bioactives Postgraduation Program, Federal Paraiba University (UFPB), João Pessoa 58051-900, PB, BrazilNatural Products and Synthetic Bioactives Postgraduation Program, Federal Paraiba University (UFPB), João Pessoa 58051-900, PB, BrazilSchool of Pharmaceutical Sciences, São Paulo State University (UNESP), Araraquara 14800-903, SP, BrazilFine Organic Chemistry Lab, School of Sciences and Technology, São Paulo State University (UNESP), Presidente Prudente 19060-080, SP, BrazilDepartment of Biochemistry and Organic Chemistry, Institute of Chemistry, São Paulo State University (UNESP), Araraquara 14800-060, SP, BrazilLeishmaniasis is a neglected tropical disease caused by a protozoan of the genus Leishmania, which has visceral and cutaneous forms. The symptoms of leishmaniasis include high fever and weakness, and the cutaneous infection also causes lesions under the skin. The drugs used to treat leishmaniasis have become less effective due to the resistance mechanisms of the protozoa. In addition, the current compounds have low selectivity for the pathogen, leading to various side effects, which results in lower adherence to treatment. Various strategies were developed to solve this problem. The bioconjugation between natural compounds with antimicrobial activity and cell-penetrating peptides could alleviate the resistance and toxicity of current treatments. This work aims to conjugate the cell penetration peptide TAT to the guanidine GVL1. The GVL1-TAT bioconjugate exhibited leishmanicidal activity against <i>Leishmania amazonensis</i> and <i>Leishmania infantum</i> with a high selectivity index. In addition, the bioconjugate was more active against the intracellular enzyme CPP than the individual compounds. This target is very important for the viability and virulence of the parasite within the host cell. Docking studies confirmed the higher interaction of the conjugate with CPP and suggested that other proteins, such as trypanothione reductase, could be targeted. Thus, the data indicated that guanidines conjugated with cell-penetrating peptides could be a good approach for developing antileishmanial molecules.https://www.mdpi.com/1420-3049/30/2/264cell penetration peptideguanidinebioconjugateLeishmaniacysteine proteaseselectivity |
| spellingShingle | João Victor Marcelino de Souza Natalia C. S. Costa Maria C. O. Arruda Brasil Luana Ribeiro dos Anjos Renata Priscila Barros de Menezes Eduardo Henrique Zampieri Jhonatan Santos de Lima Angela Maria Arenas Velasquez Luciana Scotti Marcus Tullius Scotti Marcia A. S. Graminha Eduardo R. Pérez Gonzalez Eduardo Maffud Cilli Guanidines Conjugated with Cell-Penetrating Peptides: A New Approach for the Development of Antileishmanial Molecules Molecules cell penetration peptide guanidine bioconjugate Leishmania cysteine protease selectivity |
| title | Guanidines Conjugated with Cell-Penetrating Peptides: A New Approach for the Development of Antileishmanial Molecules |
| title_full | Guanidines Conjugated with Cell-Penetrating Peptides: A New Approach for the Development of Antileishmanial Molecules |
| title_fullStr | Guanidines Conjugated with Cell-Penetrating Peptides: A New Approach for the Development of Antileishmanial Molecules |
| title_full_unstemmed | Guanidines Conjugated with Cell-Penetrating Peptides: A New Approach for the Development of Antileishmanial Molecules |
| title_short | Guanidines Conjugated with Cell-Penetrating Peptides: A New Approach for the Development of Antileishmanial Molecules |
| title_sort | guanidines conjugated with cell penetrating peptides a new approach for the development of antileishmanial molecules |
| topic | cell penetration peptide guanidine bioconjugate Leishmania cysteine protease selectivity |
| url | https://www.mdpi.com/1420-3049/30/2/264 |
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