Evidence of Guanidines Potential against <i>Leishmania (Viannia) braziliensis</i>: Exploring In Vitro Effectiveness, Toxicities and of Innate Immunity Response Effects
Leishmaniasis is a complex group of infectious and parasitic diseases that afflict many thousands of individuals across five continents. Leishmaniasis treatment remains a challenge because it relies on drugsknown for their high toxicity and limited efficacy, making itimperative to identify new molec...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-12-01
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| Series: | Biomolecules |
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| Online Access: | https://www.mdpi.com/2218-273X/14/1/26 |
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| author | Luana Ribeiro dos Anjos Vanessa Maria Rodrigues de Souza Yasmim Alves Aires Machado Vitor Moreira Partite Mohammed Aufy Geovane Dias Lopes Christian Studenik Carlos Roberto Alves Gert Lubec Eduardo Rene Perez Gonzalez Klinger Antonio da Franca Rodrigues |
| author_facet | Luana Ribeiro dos Anjos Vanessa Maria Rodrigues de Souza Yasmim Alves Aires Machado Vitor Moreira Partite Mohammed Aufy Geovane Dias Lopes Christian Studenik Carlos Roberto Alves Gert Lubec Eduardo Rene Perez Gonzalez Klinger Antonio da Franca Rodrigues |
| author_sort | Luana Ribeiro dos Anjos |
| collection | DOAJ |
| description | Leishmaniasis is a complex group of infectious and parasitic diseases that afflict many thousands of individuals across five continents. Leishmaniasis treatment remains a challenge because it relies on drugsknown for their high toxicity and limited efficacy, making itimperative to identify new molecules that offer greater effectiveness and safety. This study sought to explore the impact of seven synthetic guanidine derivatives (LQOF-G1, LQOF-G2, LQOF-G6, LQOF-G7, LQOF-G32, LQOF-G35 and LQOF-G36) onthe parasite <i>Leishmania (Viannia) braziliensis</i> and in vitro macrophage infection by this parasite, as well as cytotoxic approaches in vitro models of mammalian host cells and tissues. The synthesized compounds showed purity ≥ 99.65% and effectively inhibited parasite growth. LQOF-G1 proved the most potent, yielding the best half-maximal inhibitory concentration (IC<sub>50</sub>) values against promastigotes (4.62 μmol/L), axenic amastigotes (4.27 μmol/L), and intracellular amastigotes (3.65 μmol/L). Notably, the antileishmanial activity of LQOF-G1, LQOF-G2, and LQOF-G6 was related to immunomodulatory effects, evidenced by alterations in TNF-α, IL-12, IL-10, nitric oxide (NO), and reactive oxygen species (ROS) levels in the supernatant of culture macrophages infected with <i>L. (V.) braziliensis</i> and coincubated with these compounds. LQOF-G2 and LQOF-G36 compounds exhibited vasodilator and spasmolytic effects at higher concentrations (≥100 μmol/L). Generally, LQOF-G1, LQOF-G2, and LQOF-G32 compounds were found to be nontoxic to assessed organs and cells. No toxic effects were observed in human cell lines, such as HEK-293, CaCo-2 and A549, at concentrations ≥ 500 μmol/L. Collectively, data have shown unequivocal evidence of the effectiveness of these compounds against <i>L. (V.) braziliensis</i> parasite, one of the causative agents of Tegumentary Leishmaniasis and Mucocutaneous Leishmaniasis in America. |
| first_indexed | 2024-03-08T11:04:49Z |
| format | Article |
| id | doaj.art-e0a24240b7fc483f9c28c79c9e1dfc0d |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-03-08T11:04:49Z |
| publishDate | 2023-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-e0a24240b7fc483f9c28c79c9e1dfc0d2024-01-26T15:18:01ZengMDPI AGBiomolecules2218-273X2023-12-011412610.3390/biom14010026Evidence of Guanidines Potential against <i>Leishmania (Viannia) braziliensis</i>: Exploring In Vitro Effectiveness, Toxicities and of Innate Immunity Response EffectsLuana Ribeiro dos Anjos0Vanessa Maria Rodrigues de Souza1Yasmim Alves Aires Machado2Vitor Moreira Partite3Mohammed Aufy4Geovane Dias Lopes5Christian Studenik6Carlos Roberto Alves7Gert Lubec8Eduardo Rene Perez Gonzalez9Klinger Antonio da Franca Rodrigues10Fine Organic Chemistry Lab, School of Sciences and Technology, São Paulo State University (UNESP), Presidente Prudente 19060-080, BrazilInfectious Disease Laboratory—LADIC, Federal University of Parnaíba Delta—UFDPar, Campus Ministro Reis Velloso, São Benedito, Parnaíba 64202-020, BrazilInfectious Disease Laboratory—LADIC, Federal University of Parnaíba Delta—UFDPar, Campus Ministro Reis Velloso, São Benedito, Parnaíba 64202-020, BrazilFine Organic Chemistry Lab, School of Sciences and Technology, São Paulo State University (UNESP), Presidente Prudente 19060-080, BrazilDepartment of Pharmaceutical Sciences, Division of Pharmacology and Toxicology, University of Vienna, Josef Holaubek Platz 2, UZAII (2D 259), 1090 Vienna, AustriaLaboratório de Biologia Molecular e Doenças Endêmicas, Fundação Oswaldo Cruz, Instituto Oswaldo Cruz, 4365, Manguinhos, Rio de Janeiro 21040-900, BrazilDepartment of Pharmaceutical Sciences, Division of Pharmacology and Toxicology, University of Vienna, Josef Holaubek Platz 2, UZAII (2D 259), 1090 Vienna, AustriaLaboratório de Biologia Molecular e Doenças Endêmicas, Fundação Oswaldo Cruz, Instituto Oswaldo Cruz, 4365, Manguinhos, Rio de Janeiro 21040-900, BrazilDepartment of Neuroproteomics, Paracelsus Medical University, 5020 Salzburg, AustriaFine Organic Chemistry Lab, School of Sciences and Technology, São Paulo State University (UNESP), Presidente Prudente 19060-080, BrazilInfectious Disease Laboratory—LADIC, Federal University of Parnaíba Delta—UFDPar, Campus Ministro Reis Velloso, São Benedito, Parnaíba 64202-020, BrazilLeishmaniasis is a complex group of infectious and parasitic diseases that afflict many thousands of individuals across five continents. Leishmaniasis treatment remains a challenge because it relies on drugsknown for their high toxicity and limited efficacy, making itimperative to identify new molecules that offer greater effectiveness and safety. This study sought to explore the impact of seven synthetic guanidine derivatives (LQOF-G1, LQOF-G2, LQOF-G6, LQOF-G7, LQOF-G32, LQOF-G35 and LQOF-G36) onthe parasite <i>Leishmania (Viannia) braziliensis</i> and in vitro macrophage infection by this parasite, as well as cytotoxic approaches in vitro models of mammalian host cells and tissues. The synthesized compounds showed purity ≥ 99.65% and effectively inhibited parasite growth. LQOF-G1 proved the most potent, yielding the best half-maximal inhibitory concentration (IC<sub>50</sub>) values against promastigotes (4.62 μmol/L), axenic amastigotes (4.27 μmol/L), and intracellular amastigotes (3.65 μmol/L). Notably, the antileishmanial activity of LQOF-G1, LQOF-G2, and LQOF-G6 was related to immunomodulatory effects, evidenced by alterations in TNF-α, IL-12, IL-10, nitric oxide (NO), and reactive oxygen species (ROS) levels in the supernatant of culture macrophages infected with <i>L. (V.) braziliensis</i> and coincubated with these compounds. LQOF-G2 and LQOF-G36 compounds exhibited vasodilator and spasmolytic effects at higher concentrations (≥100 μmol/L). Generally, LQOF-G1, LQOF-G2, and LQOF-G32 compounds were found to be nontoxic to assessed organs and cells. No toxic effects were observed in human cell lines, such as HEK-293, CaCo-2 and A549, at concentrations ≥ 500 μmol/L. Collectively, data have shown unequivocal evidence of the effectiveness of these compounds against <i>L. (V.) braziliensis</i> parasite, one of the causative agents of Tegumentary Leishmaniasis and Mucocutaneous Leishmaniasis in America.https://www.mdpi.com/2218-273X/14/1/26guanidine derivatives<i>Leishmania (Viannia) braziliensis</i>immunomodulationorgan and cell toxicity |
| spellingShingle | Luana Ribeiro dos Anjos Vanessa Maria Rodrigues de Souza Yasmim Alves Aires Machado Vitor Moreira Partite Mohammed Aufy Geovane Dias Lopes Christian Studenik Carlos Roberto Alves Gert Lubec Eduardo Rene Perez Gonzalez Klinger Antonio da Franca Rodrigues Evidence of Guanidines Potential against <i>Leishmania (Viannia) braziliensis</i>: Exploring In Vitro Effectiveness, Toxicities and of Innate Immunity Response Effects Biomolecules guanidine derivatives <i>Leishmania (Viannia) braziliensis</i> immunomodulation organ and cell toxicity |
| title | Evidence of Guanidines Potential against <i>Leishmania (Viannia) braziliensis</i>: Exploring In Vitro Effectiveness, Toxicities and of Innate Immunity Response Effects |
| title_full | Evidence of Guanidines Potential against <i>Leishmania (Viannia) braziliensis</i>: Exploring In Vitro Effectiveness, Toxicities and of Innate Immunity Response Effects |
| title_fullStr | Evidence of Guanidines Potential against <i>Leishmania (Viannia) braziliensis</i>: Exploring In Vitro Effectiveness, Toxicities and of Innate Immunity Response Effects |
| title_full_unstemmed | Evidence of Guanidines Potential against <i>Leishmania (Viannia) braziliensis</i>: Exploring In Vitro Effectiveness, Toxicities and of Innate Immunity Response Effects |
| title_short | Evidence of Guanidines Potential against <i>Leishmania (Viannia) braziliensis</i>: Exploring In Vitro Effectiveness, Toxicities and of Innate Immunity Response Effects |
| title_sort | evidence of guanidines potential against i leishmania viannia braziliensis i exploring in vitro effectiveness toxicities and of innate immunity response effects |
| topic | guanidine derivatives <i>Leishmania (Viannia) braziliensis</i> immunomodulation organ and cell toxicity |
| url | https://www.mdpi.com/2218-273X/14/1/26 |
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