{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T13:28:10Z","timestamp":1777469290218,"version":"3.51.4"},"reference-count":50,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2022,11,30]],"date-time":"2022-11-30T00:00:00Z","timestamp":1669766400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"CNPq","award":["562655\/2010-7"],"award-info":[{"award-number":["562655\/2010-7"]}]},{"name":"CNPq","award":["312505\/2021-3"],"award-info":[{"award-number":["312505\/2021-3"]}]},{"name":"CNPq","award":["2017\/15840-0"],"award-info":[{"award-number":["2017\/15840-0"]}]},{"name":"CNPq","award":["2021\/04876-4"],"award-info":[{"award-number":["2021\/04876-4"]}]},{"name":"CNPq","award":["0002\/2014"],"award-info":[{"award-number":["0002\/2014"]}]},{"name":"FAPESP","award":["562655\/2010-7"],"award-info":[{"award-number":["562655\/2010-7"]}]},{"name":"FAPESP","award":["312505\/2021-3"],"award-info":[{"award-number":["312505\/2021-3"]}]},{"name":"FAPESP","award":["2017\/15840-0"],"award-info":[{"award-number":["2017\/15840-0"]}]},{"name":"FAPESP","award":["2021\/04876-4"],"award-info":[{"award-number":["2021\/04876-4"]}]},{"name":"FAPESP","award":["0002\/2014"],"award-info":[{"award-number":["0002\/2014"]}]},{"name":"PRONEX","award":["562655\/2010-7"],"award-info":[{"award-number":["562655\/2010-7"]}]},{"name":"PRONEX","award":["312505\/2021-3"],"award-info":[{"award-number":["312505\/2021-3"]}]},{"name":"PRONEX","award":["2017\/15840-0"],"award-info":[{"award-number":["2017\/15840-0"]}]},{"name":"PRONEX","award":["2021\/04876-4"],"award-info":[{"award-number":["2021\/04876-4"]}]},{"name":"PRONEX","award":["0002\/2014"],"award-info":[{"award-number":["0002\/2014"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>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\u2013156). The evaluated N-acyl hydrazones did not show cytotoxicity at the tested concentrations, presenting CC50 values greater than 50 \u00b5M. 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 &lt; 0.05) the production of nitrite, TNF-\u03b1, and IL-1\u03b2. Interestingly, both molecules significantly reduced the production of IL-2 and IFN-\u03b3 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.<\/jats:p>","DOI":"10.3390\/molecules27238343","type":"journal-article","created":{"date-parts":[[2022,11,30]],"date-time":"2022-11-30T07:38:50Z","timestamp":1669793930000},"page":"8343","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Molecular Hybridization Strategy on the Design, Synthesis, and Structural Characterization of Ferrocene-N-acyl Hydrazones as Immunomodulatory Agents"],"prefix":"10.3390","volume":"27","author":[{"given":"La\u00eds Peres","family":"Silva","sequence":"first","affiliation":[{"name":"Department of Life Sciences, State University of Bahia (UNEB), Salvador 41150-000, BA, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ivanilson Pimenta","family":"Santos","sequence":"additional","affiliation":[{"name":"Gon\u00e7alo Moniz Institute, Oswaldo Cruz Foundation (IGM-FIOCRUZ\/BA), Salvador 40296-710, BA, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dahara Keyse Carvalho","family":"Silva","sequence":"additional","affiliation":[{"name":"Gon\u00e7alo Moniz Institute, Oswaldo Cruz Foundation (IGM-FIOCRUZ\/BA), Salvador 40296-710, BA, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bruna Padilha Zurita Claro","family":"dos Reis","sequence":"additional","affiliation":[{"name":"Gon\u00e7alo Moniz Institute, Oswaldo Cruz Foundation (IGM-FIOCRUZ\/BA), Salvador 40296-710, BA, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C\u00e1ssio Santana","family":"Meira","sequence":"additional","affiliation":[{"name":"Department of Life Sciences, State University of Bahia (UNEB), Salvador 41150-000, BA, Brazil"},{"name":"Gon\u00e7alo Moniz Institute, Oswaldo Cruz Foundation (IGM-FIOCRUZ\/BA), Salvador 40296-710, BA, Brazil"},{"name":"Institute for Innovation in Advanced Health Systems (CIMATEC ISI SAS\u2014University Center SENAI\/CIMATEC), Salvador 41650-010, BA, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marcos Ven\u00edcius Batista de Souza","family":"Castro","sequence":"additional","affiliation":[{"name":"Laboratory of Design and Synthesis Applied to Medicinal Chemistry-SintMed\u00ae, Center for Technology and Geosciences, Federal University of Pernambuco, Recife 50740-521, PE, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jos\u00e9 Maur\u00edcio","family":"dos Santos Filho","sequence":"additional","affiliation":[{"name":"Laboratory of Design and Synthesis Applied to Medicinal Chemistry-SintMed\u00ae, Center for Technology and Geosciences, Federal University of Pernambuco, Recife 50740-521, PE, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1127-6083","authenticated-orcid":false,"given":"Jo\u00e3o Honorato de","family":"Araujo-Neto","sequence":"additional","affiliation":[{"name":"Multiuser Laboratory of Structural Crystallography, Institute of S\u00e3o Carlos, University of S\u00e3o Paulo, S\u00e3o Carlos 13566-590, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Javier Alcides","family":"Ellena","sequence":"additional","affiliation":[{"name":"Multiuser Laboratory of Structural Crystallography, Institute of S\u00e3o Carlos, University of S\u00e3o Paulo, S\u00e3o Carlos 13566-590, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1250-552X","authenticated-orcid":false,"given":"Rafael Gomes da","family":"Silveira","sequence":"additional","affiliation":[{"name":"Multiuser Laboratory of Structural Crystallography, Institute of S\u00e3o Carlos, University of S\u00e3o Paulo, S\u00e3o Carlos 13566-590, SP, Brazil"},{"name":"Department of Chemistry, Federal Institute of Goi\u00e1s, Campus Ceres, Ceres 76300-000, GO, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Milena Botelho Pereira","family":"Soares","sequence":"additional","affiliation":[{"name":"Gon\u00e7alo Moniz Institute, Oswaldo Cruz Foundation (IGM-FIOCRUZ\/BA), Salvador 40296-710, BA, Brazil"},{"name":"Institute for Innovation in Advanced Health Systems (CIMATEC ISI SAS\u2014University Center SENAI\/CIMATEC), Salvador 41650-010, BA, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1016\/j.molcel.2014.03.030","article-title":"Stress, inflammation, and defense of homeostasis","volume":"54","author":"Chovatiya","year":"2014","journal-title":"Mol. 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