{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T02:58:10Z","timestamp":1784257090508,"version":"3.55.0"},"reference-count":58,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2020,4,8]],"date-time":"2020-04-08T00:00:00Z","timestamp":1586304000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005669","name":"Funda\u00e7\u00e3o de Apoio \u00e0 Pesquisa do Estado da Para\u00edba","doi-asserted-by":"publisher","award":["88887.214956\/2018-00"],"award-info":[{"award-number":["88887.214956\/2018-00"]}],"id":[{"id":"10.13039\/501100005669","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The compound (E)-2-cyano-3-(1H-indol-3-yl)-N-phenylacrylamide (ICMD-01) was designed and developed based on the structures of clinically relevant drugs indomethacin and paracetamol through the molecular hybridization strategy. This derivative was obtained by an amidation reaction between substituted anilines and ethyl 2-cyanoacetate followed by a Knoevenagel-type condensation reaction with indole aldehyde that resulted in both a viable synthesis and satisfactory yield. In order to assess the immunomodulatory and anti-inflammatory activity, in vitro assays were performed in J774 macrophages, and significant inhibitions (p &lt; 0.05) of the production of nitrite and the production of cytokines (IL-1\u03b2 and TNF\u03b1) in noncytotoxic concentrations were observed. The anti-inflammatory effect was also studied via CFA-induced paw edema in vivo tests and zymosan-induced peritonitis. In the paw edema assay, ICMD01 (50 mg kg\u22121) showed satisfactory activity, as did the group treated with dexamethasone, reducing edema in 2\u20136 h. In addition, there was no significant inhibition of PGE2, IL-1\u03b2 or TNF\u03b1 in vivo. Moreover, in the peritonitis assay that assesses leukocyte migration, ICMD-01 exhibited promising results. Therefore, these preliminary studies demonstrate this compound to be a strong candidate for an anti-inflammatory drug together with an improved gastrointestinal safety profile when compared to the conventional anti-inflammatory drugs.<\/jats:p>","DOI":"10.3390\/ijms21072591","type":"journal-article","created":{"date-parts":[[2020,4,9]],"date-time":"2020-04-09T03:40:19Z","timestamp":1586403619000},"page":"2591","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["(E)-2-Cyano-3-(1H-Indol-3-yl)-N-Phenylacrylamide, a Hybrid Compound Derived from Indomethacin and Paracetamol: Design, Synthesis and Evaluation of the Anti-Inflammatory Potential"],"prefix":"10.3390","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8354-3198","authenticated-orcid":false,"given":"Pablo","family":"Silva","sequence":"first","affiliation":[{"name":"Programa de P\u00f3s-Gradua\u00e7\u00e3o em Ci\u00eancias Farmac\u00eauticas, Universidade Estadual da Para\u00edba, Campina Grande 58429-500, PB, Brazil"},{"name":"Laborat\u00f3rio de Ensaios Farmacol\u00f3gicos, Departamento de Farm\u00e1cia, Universidade Estadual da Para\u00edba, Campina Grande 58429-500, PB, Brazil"},{"name":"Laborat\u00f3rio de Desenvolvimento e S\u00edntese de F\u00e1rmacos, Departamento de Farm\u00e1cia, Universidade Estadual da Paraiba, Campina Grande 58429-500, PB, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"de Almeida","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Ensaios Farmacol\u00f3gicos, Departamento de Farm\u00e1cia, Universidade Estadual da Para\u00edba, Campina Grande 58429-500, PB, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9461-2478","authenticated-orcid":false,"given":"Jamire","family":"Silva","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Desenvolvimento e S\u00edntese de F\u00e1rmacos, Departamento de Farm\u00e1cia, Universidade Estadual da Paraiba, Campina Grande 58429-500, PB, Brazil"},{"name":"Programa de P\u00f3s-Gradua\u00e7\u00e3o em Ci\u00eancias Farmac\u00eauticas, Universidade Federal de Pernambuco, Recife 58429-500, PE, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2904-036X","authenticated-orcid":false,"given":"Sonaly","family":"Albino","sequence":"additional","affiliation":[{"name":"Programa de P\u00f3s-Gradua\u00e7\u00e3o em Ci\u00eancias Farmac\u00eauticas, Universidade Estadual da Para\u00edba, Campina Grande 58429-500, PB, Brazil"},{"name":"Laborat\u00f3rio de Desenvolvimento e S\u00edntese de F\u00e1rmacos, Departamento de Farm\u00e1cia, Universidade Estadual da Paraiba, Campina Grande 58429-500, PB, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renan","family":"Esp\u00edrito-Santo","sequence":"additional","affiliation":[{"name":"Instituto Gon\u00e7alo Moniz, Funda\u00e7\u00e3o Oswaldo Cruz, Salvador 40296-710, BA, Brazil"},{"name":"Faculdade de Farm\u00e1cia, Universidade Federal da Bahia, Salvador 40170-290, BA, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Lima","sequence":"additional","affiliation":[{"name":"Programa de P\u00f3s-Gradua\u00e7\u00e3o em Ci\u00eancias Farmac\u00eauticas, Universidade Federal de Pernambuco, Recife 58429-500, PE, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0113-7864","authenticated-orcid":false,"given":"Cristiane","family":"Villarreal","sequence":"additional","affiliation":[{"name":"Instituto Gon\u00e7alo Moniz, Funda\u00e7\u00e3o Oswaldo Cruz, Salvador 40296-710, BA, Brazil"},{"name":"Faculdade de Farm\u00e1cia, Universidade Federal da Bahia, Salvador 40170-290, BA, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1590-3750","authenticated-orcid":false,"given":"Ricardo","family":"Moura","sequence":"additional","affiliation":[{"name":"Programa de P\u00f3s-Gradua\u00e7\u00e3o em Ci\u00eancias Farmac\u00eauticas, Universidade Estadual da Para\u00edba, Campina Grande 58429-500, PB, Brazil"},{"name":"Laborat\u00f3rio de Desenvolvimento e S\u00edntese de F\u00e1rmacos, Departamento de Farm\u00e1cia, Universidade Estadual da Paraiba, Campina Grande 58429-500, PB, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6083-5390","authenticated-orcid":false,"given":"Vanda","family":"Santos","sequence":"additional","affiliation":[{"name":"Programa de P\u00f3s-Gradua\u00e7\u00e3o em Ci\u00eancias Farmac\u00eauticas, Universidade Estadual da Para\u00edba, Campina Grande 58429-500, PB, Brazil"},{"name":"Laborat\u00f3rio de Ensaios Farmacol\u00f3gicos, 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