Molecular hybridization strategy on the design, synthesis, and structural characterization of ferrocene-n-acyl hydrazones as immunomodulatory agents

dc.creatorSilva, Laís Peres
dc.creatorSantos, Ivanilson Pimenta
dc.creatorSilva, Dahara Keyse Carvalho
dc.creatorReis, Bruna Padilha Zurita Claro dos
dc.creatorMeira, Cássio Santana
dc.creatorCastro, Marcos Venícius Batista de Souza
dc.creatorSantos Filho, José Maurício dos
dc.creatorAraujo Neto, João Honorato de
dc.creatorEllena, Javier Alcides
dc.creatorSilveira, Rafael Gomes da
dc.creatorSoares, Milena Botelho Pereira
dc.date2023-02-09T19:43:50Z
dc.date2023-02-09T19:43:50Z
dc.date2022
dc.date.accessioned2023-09-26T21:03:11Z
dc.date.available2023-09-26T21:03:11Z
dc.identifierSILVA, 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.
dc.identifier1420-3049
dc.identifierhttps://www.arca.fiocruz.br/handle/icict/56995
dc.identifier10.3390/molecules27238343
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/8868373
dc.descriptionConselho 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).
dc.descriptionImmunomodulatory 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.
dc.formatapplication/pdf
dc.languageeng
dc.publisherMDPI
dc.rightsopen access
dc.subjectImmunomodulation
dc.subjectImunomodulação
dc.subjectChoque endotóxico
dc.subjectPeritonite aguda
dc.subjectN-acil hidrazonas
dc.subjectFerroceno
dc.subjectImmunomodulation
dc.subjectEndotoxic shock
dc.subjectAcute peritonitis
dc.subjectN-acyl hydrazones
dc.subjectferrocene
dc.titleMolecular hybridization strategy on the design, synthesis, and structural characterization of ferrocene-n-acyl hydrazones as immunomodulatory agents
dc.typeArticle


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