| Author | Silva, Laís Peres | |
| Author | Santos, Ivanilson Pimenta | |
| Author | Silva, Dahara Keyse Carvalho | |
| Author | Reis, Bruna Padilha Zurita Claro dos | |
| Author | Meira, Cássio Santana | |
| Author | Castro, Marcos Venícius Batista de Souza | |
| Author | Santos Filho, José Maurício dos | |
| Author | Araujo Neto, João Honorato de | |
| Author | Ellena, Javier Alcides | |
| Author | Silveira, Rafael Gomes da | |
| Author | Soares, Milena Botelho Pereira | |
| Access date | 2023-02-09T19:43:50Z | |
| Available date | 2023-02-09T19:43:50Z | |
| Document date | 2022 | |
| Citation | SILVA, Laís Peres et al. Molecular hybridization strategy on the design, synthesis, and structural characterization of ferrocene-n-acyl hydrazones as immunomodulatory agents. Molecules, v. 27, p. 1-22, 2022. | en_US |
| ISSN | 1420-3049 | en_US |
| URI | https://www.arca.fiocruz.br/handle/icict/56995 | |
| Sponsorship | Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq).
Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP).
Programa de Apoio a Núcleos de Excelência (Pronex). | en_US |
| Language | eng | en_US |
| Publisher | MDPI | en_US |
| Rights | open access | en_US |
| MeSH | Immunomodulation | en_US |
| Subject in Portuguese | Imunomodulação | en_US |
| Subject in Portuguese | Choque endotóxico | en_US |
| Subject in Portuguese | Peritonite aguda | en_US |
| Subject in Portuguese | N-acil hidrazonas | en_US |
| Subject in Portuguese | Ferroceno | en_US |
| Title | Molecular hybridization strategy on the design, synthesis, and structural characterization of ferrocene-n-acyl hydrazones as immunomodulatory agents | en_US |
| Type | Article | en_US |
| DOI | 10.3390/molecules27238343 | |
| Abstract | 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-N-acyl hydrazones derivatives (SintMed(141–156). The evaluated N-acyl hydrazones did not show cytotoxicity at the tested concentrations, presenting CC50 values greater than 50 µM. In addition, all ferrocenyl-N-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-N-acyl hydrazones SintMed149 and SintMed150 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 (p < 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, SintMed150 did not show signs of acute toxicity in animals treated with 50 or 100 mg/kg. Finally, we observed that ferrocenyl-N-acyl hydrazone SintMed150 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. | en_US |
| Affilliation | Universidade Estadual da Bahia. Departamento de Ciências da Vida. Salvador, BA, Brasil. | en_US |
| Affilliation | Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil. | en_US |
| Affilliation | Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil. | en_US |
| Affilliation | Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil. | en_US |
| Affilliation | Universidade Estadual da Bahia. Departamento de Ciências da Vida. Salvador, BA, Brasil / Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Instituto de Inovação em Sistemas Avançados de Saúda. Centro Universitário SENAI/CIMATEC. Salvador, BA, Brasil. | en_US |
| Affilliation | Universidade Federal de Pernambuco. Centro de Tecnologia e Geociências. Laboratório de Desenho e Síntese Aplicada à Química Medicinal-SintMed. Recife, PE, Brasil. | en_US |
| Affilliation | Universidade Federal de Pernambuco. Centro de Tecnologia e Geociências. Laboratório de Desenho e Síntese Aplicada à Química Medicinal-SintMed. Recife, PE, Brasil. | en_US |
| Affilliation | Universidade de São Paulo. Instituto de São Carlos. Laboratório Multiusuário de Cristalografia Estrutural. São Carlos, SP, Brasil. | en_US |
| Affilliation | Universidade de São Paulo. Instituto de São Carlos. Laboratório Multiusuário de Cristalografia Estrutural. São Carlos, SP, Brasil. | en_US |
| Affilliation | Universidade de São Paulo. Instituto de São Carlos. Laboratório Multiusuário de Cristalografia Estrutural. São Carlos, SP, Brasil / Instituto Federal de Goiás. Departamento de Química. Ceres, GO, Brasil. | en_US |
| Affilliation | Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Instituto de Inovação em Sistemas Avançados de Saúda. Centro Universitário SENAI/CIMATEC. Salvador, BA, Brasil. | en_US |
| Subject | Immunomodulation | en_US |
| Subject | Endotoxic shock | en_US |
| Subject | Acute peritonitis | en_US |
| Subject | N-acyl hydrazones | en_US |
| Subject | ferrocene | en_US |
