Article
Molecular hybridization strategy on the design, synthesis, and structural characterization of ferrocene-n-acyl hydrazones as immunomodulatory agents
Registro en:
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.
1420-3049
10.3390/molecules27238343
Autor
Silva, Laís Peres
Santos, Ivanilson Pimenta
Silva, Dahara Keyse Carvalho
Reis, Bruna Padilha Zurita Claro dos
Meira, Cássio Santana
Castro, Marcos Venícius Batista de Souza
Santos Filho, José Maurício dos
Araujo Neto, João Honorato de
Ellena, Javier Alcides
Silveira, Rafael Gomes da
Soares, Milena Botelho Pereira
Resumen
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). 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.