title: Synthesis and pharmacological evaluation of pyrazine N-acylhydrazone derivatives designed as novel analgesic and anti-inflammatory drug candidates.
abstract: In this paper, we report the synthesis and pharmacological evaluation of pyrazine N-acylhydrazone (NAH) derivatives (2a-s) designed as novel analgesic and anti-inflammatory drug candidates. This series was planned by molecular simplification of prototype 1 (LASSBio-1018), previously described as a non-selective cyclooxygenase inhibitor. Derivatives 2a-s were evaluated in several animal models of pain and inflammation, standing-out compound 2o (2-N'-[(E)-(3,4,5-trimethoxyphenyl) methylidene]-2-pyrazinecarbohydrazide; LASSBio-1181), that was also active in a murine model of chronic inflammation (i.e., adjuvant-induced arthritis test in rats) and can be considered a new analgesic and anti-inflammatory lead for drug development.
authors.affiliation: LaFI-Laboratório de Farmacologia e Imunidade, Instituto de Ciências Biológicas e da Saúde, Universidade Federal de Alagoas, Maceió, AL, Brazil.
authors.forename: Yolanda Karla Cupertino
authors.initials: YK
authors.lastname: da Silva
authors.forename: Cristina Villarinho
authors.initials: CV
authors.lastname: Augusto
authors.forename: Maria Letícia
authors.initials: ML
authors.lastname: de Castro Barbosa
authors.forename: Gabriela Muniz
authors.initials: GM
authors.lastname: de Albuquerque Melo
authors.forename: Aline Cavalcanti
authors.initials: AC
authors.lastname: de Queiroz
authors.forename: Thays
authors.initials: T
authors.lastname: de Lima Matos Freire Dias
authors.forename: Walfrido Bispo
authors.initials: WB
authors.lastname: Júnior
authors.forename: Eliezer J
authors.initials: EJ
authors.lastname: Barreiro
authors.forename: Lídia Moreira
authors.initials: LM
authors.lastname: Lima
authors.forename: Magna Suzana
authors.initials: MS
authors.lastname: Alexandre-Moreira
mesh_terms: D000700:Analgesics / Q000138:chemical synthesis / Q000737:chemistry* / Q000627:therapeutic use*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000627:therapeutic use*; D001168:Arthritis / Q000139:chemically induced / Q000188:drug therapy*; D004423:Ear / Q000473:pathology; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy; D005260:Female; D005620:Freund's Adjuvant; D006835:Hydrazones / Q000138:chemical synthesis / Q000737:chemistry* / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D010146:Pain / Q000188:drug therapy*; D010538:Peritonitis / Q000139:chemically induced / Q000188:drug therapy; D011719:Pyrazines / Q000138:chemical synthesis / Q000737:chemistry* / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D015054:Zymosan
chemical_list: D000700:Analgesics; D000893:Anti-Inflammatory Agents; D006835:Hydrazones; D011719:Pyrazines; D005620:Freund's Adjuvant; D015054:Zymosan