Molecular Hybridization Strategy on the Design, Synthesis, and Structural Characterization of Ferrocene-<i>N</i>-acyl Hydrazones as Immunomodulatory Agents
Immunomodulatory agents are widely used for the treatment of immune-mediated diseases, but the range of side effects of the available drugs makes necessary the search for new immunomodulatory drugs. Here, we investigated the immunomodulatory activity of new ferrocenyl-<i>N</i>-acyl hydra...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-11-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/27/23/8343 |
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| author | Laís Peres Silva Ivanilson Pimenta Santos Dahara Keyse Carvalho Silva Bruna Padilha Zurita Claro dos Reis Cássio Santana Meira Marcos Venícius Batista de Souza Castro José Maurício dos Santos Filho João Honorato de Araujo-Neto Javier Alcides Ellena Rafael Gomes da Silveira Milena Botelho Pereira Soares |
| author_facet | Laís Peres Silva Ivanilson Pimenta Santos Dahara Keyse Carvalho Silva Bruna Padilha Zurita Claro dos Reis Cássio Santana Meira Marcos Venícius Batista de Souza Castro José Maurício dos Santos Filho João Honorato de Araujo-Neto Javier Alcides Ellena Rafael Gomes da Silveira Milena Botelho Pereira Soares |
| author_sort | Laís Peres Silva |
| collection | DOAJ |
| description | Immunomodulatory agents are widely used for the treatment of immune-mediated diseases, but the range of side effects of the available drugs makes necessary the search for new immunomodulatory drugs. Here, we investigated the immunomodulatory activity of new ferrocenyl-<i>N</i>-acyl hydrazones derivatives (<b>SintMed</b>(<b>141</b>–<b>156</b>). The evaluated <i>N</i>-acyl hydrazones did not show cytotoxicity at the tested concentrations, presenting CC<sub>50</sub> values greater than 50 µM. In addition, all ferrocenyl-<i>N</i>-acyl hydrazones modulated nitrite production in immortalized macrophages, showing inhibition values between 14.4% and 74.2%. By presenting a better activity profile, the ferrocenyl-<i>N</i>-acyl hydrazones <b>SintMed149</b> and <b>SintMed150</b> also had their cytotoxicity and anti-inflammatory effect evaluated in cultures of peritoneal macrophages. The molecules were not cytotoxic at any of the concentrations tested in peritoneal macrophages and were able to significantly reduce (<i>p</i> < 0.05) the production of nitrite, TNF-α, and IL-1β. Interestingly, both molecules significantly reduced the production of IL-2 and IFN-γ in cultured splenocytes activated with concanavalin A. Moreover, <b>SintMed150</b> did not show signs of acute toxicity in animals treated with 50 or 100 mg/kg. Finally, we observed that ferrocenyl-<i>N</i>-acyl hydrazone <b>SintMed150</b> at 100 mg/kg reduced the migration of neutrophils (44.6%) in an acute peritonitis model and increased animal survival by 20% in an LPS-induced endotoxic shock model. These findings suggest that such compounds have therapeutic potential to be used to treat diseases of inflammatory origin. |
| first_indexed | 2024-03-09T17:39:32Z |
| format | Article |
| id | doaj.art-4d92303968264f71a971be6a169fdcc9 |
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| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-09T17:39:32Z |
| publishDate | 2022-11-01 |
| publisher | MDPI AG |
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| series | Molecules |
| spelling | doaj.art-4d92303968264f71a971be6a169fdcc92023-11-24T11:40:41ZengMDPI AGMolecules1420-30492022-11-012723834310.3390/molecules27238343Molecular Hybridization Strategy on the Design, Synthesis, and Structural Characterization of Ferrocene-<i>N</i>-acyl Hydrazones as Immunomodulatory AgentsLaís Peres Silva0Ivanilson Pimenta Santos1Dahara Keyse Carvalho Silva2Bruna Padilha Zurita Claro dos Reis3Cássio Santana Meira4Marcos Venícius Batista de Souza Castro5José Maurício dos Santos Filho6João Honorato de Araujo-Neto7Javier Alcides Ellena8Rafael Gomes da Silveira9Milena Botelho Pereira Soares10Department of Life Sciences, State University of Bahia (UNEB), Salvador 41150-000, BA, BrazilGonçalo Moniz Institute, Oswaldo Cruz Foundation (IGM-FIOCRUZ/BA), Salvador 40296-710, BA, BrazilGonçalo Moniz Institute, Oswaldo Cruz Foundation (IGM-FIOCRUZ/BA), Salvador 40296-710, BA, BrazilGonçalo Moniz Institute, Oswaldo Cruz Foundation (IGM-FIOCRUZ/BA), Salvador 40296-710, BA, BrazilDepartment of Life Sciences, State University of Bahia (UNEB), Salvador 41150-000, BA, BrazilLaboratory of Design and Synthesis Applied to Medicinal Chemistry-SintMed®, Center for Technology and Geosciences, Federal University of Pernambuco, Recife 50740-521, PE, BrazilLaboratory of Design and Synthesis Applied to Medicinal Chemistry-SintMed®, Center for Technology and Geosciences, Federal University of Pernambuco, Recife 50740-521, PE, BrazilMultiuser Laboratory of Structural Crystallography, Institute of São Carlos, University of São Paulo, São Carlos 13566-590, SP, BrazilMultiuser Laboratory of Structural Crystallography, Institute of São Carlos, University of São Paulo, São Carlos 13566-590, SP, BrazilMultiuser Laboratory of Structural Crystallography, Institute of São Carlos, University of São Paulo, São Carlos 13566-590, SP, BrazilGonçalo Moniz Institute, Oswaldo Cruz Foundation (IGM-FIOCRUZ/BA), Salvador 40296-710, BA, BrazilImmunomodulatory agents are widely used for the treatment of immune-mediated diseases, but the range of side effects of the available drugs makes necessary the search for new immunomodulatory drugs. Here, we investigated the immunomodulatory activity of new ferrocenyl-<i>N</i>-acyl hydrazones derivatives (<b>SintMed</b>(<b>141</b>–<b>156</b>). The evaluated <i>N</i>-acyl hydrazones did not show cytotoxicity at the tested concentrations, presenting CC<sub>50</sub> values greater than 50 µM. In addition, all ferrocenyl-<i>N</i>-acyl hydrazones modulated nitrite production in immortalized macrophages, showing inhibition values between 14.4% and 74.2%. By presenting a better activity profile, the ferrocenyl-<i>N</i>-acyl hydrazones <b>SintMed149</b> and <b>SintMed150</b> also had their cytotoxicity and anti-inflammatory effect evaluated in cultures of peritoneal macrophages. The molecules were not cytotoxic at any of the concentrations tested in peritoneal macrophages and were able to significantly reduce (<i>p</i> < 0.05) the production of nitrite, TNF-α, and IL-1β. Interestingly, both molecules significantly reduced the production of IL-2 and IFN-γ in cultured splenocytes activated with concanavalin A. Moreover, <b>SintMed150</b> did not show signs of acute toxicity in animals treated with 50 or 100 mg/kg. Finally, we observed that ferrocenyl-<i>N</i>-acyl hydrazone <b>SintMed150</b> at 100 mg/kg reduced the migration of neutrophils (44.6%) in an acute peritonitis model and increased animal survival by 20% in an LPS-induced endotoxic shock model. These findings suggest that such compounds have therapeutic potential to be used to treat diseases of inflammatory origin.https://www.mdpi.com/1420-3049/27/23/8343immunomodulationendotoxic shockacute peritonitis<i>N</i>-acyl hydrazonesferrocene |
| spellingShingle | Laís Peres Silva Ivanilson Pimenta Santos Dahara Keyse Carvalho Silva Bruna Padilha Zurita Claro dos Reis Cássio Santana Meira Marcos Venícius Batista de Souza Castro José Maurício dos Santos Filho João Honorato de Araujo-Neto Javier Alcides Ellena Rafael Gomes da Silveira Milena Botelho Pereira Soares Molecular Hybridization Strategy on the Design, Synthesis, and Structural Characterization of Ferrocene-<i>N</i>-acyl Hydrazones as Immunomodulatory Agents Molecules immunomodulation endotoxic shock acute peritonitis <i>N</i>-acyl hydrazones ferrocene |
| title | Molecular Hybridization Strategy on the Design, Synthesis, and Structural Characterization of Ferrocene-<i>N</i>-acyl Hydrazones as Immunomodulatory Agents |
| title_full | Molecular Hybridization Strategy on the Design, Synthesis, and Structural Characterization of Ferrocene-<i>N</i>-acyl Hydrazones as Immunomodulatory Agents |
| title_fullStr | Molecular Hybridization Strategy on the Design, Synthesis, and Structural Characterization of Ferrocene-<i>N</i>-acyl Hydrazones as Immunomodulatory Agents |
| title_full_unstemmed | Molecular Hybridization Strategy on the Design, Synthesis, and Structural Characterization of Ferrocene-<i>N</i>-acyl Hydrazones as Immunomodulatory Agents |
| title_short | Molecular Hybridization Strategy on the Design, Synthesis, and Structural Characterization of Ferrocene-<i>N</i>-acyl Hydrazones as Immunomodulatory Agents |
| title_sort | molecular hybridization strategy on the design synthesis and structural characterization of ferrocene i n i acyl hydrazones as immunomodulatory agents |
| topic | immunomodulation endotoxic shock acute peritonitis <i>N</i>-acyl hydrazones ferrocene |
| url | https://www.mdpi.com/1420-3049/27/23/8343 |
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