title: Novel 6-methanesulfonamide-3,4-methylenedioxyphenyl-N-acylhydrazones: orally effective anti-inflammatory drug candidates.
abstract: We described herein the molecular design of novel in vivo anti-inflammatory 6-methanesulfonamide-3,4-methylenedioxyphenyl-N-acylhydrazone derivatives (1) planned by applying the molecular hybridization approach. This work also points out to the discovery of LASSBio-930 (1c) as a novel anti-inflammatory and anti-hyperalgesic prototype, which was able to reduce carrageenan-induced rat paw edema with an ED(50) of 97.8 micromol/kg, acting mainly as a non-selective COX inhibitor.
authors.affiliation: LASSBio-Laboratório de Avaliação e Síntese de Substâncias Bioativas, Faculdade de Farmácia, Universidade Federal do Rio de Janeiro, PO Box 68023, 21941-902 Rio de Janeiro, RJ, Brazil.
authors.forename: Jorge L M
authors.initials: JL
authors.lastname: Tributino
authors.forename: Carolina D
authors.initials: CD
authors.lastname: Duarte
authors.forename: Rodrigo S
authors.initials: RS
authors.lastname: Corrêa
authors.forename: Antonio C
authors.initials: AC
authors.lastname: Doriguetto
authors.forename: Javier
authors.initials: J
authors.lastname: Ellena
authors.forename: Nelilma C
authors.initials: NC
authors.lastname: Romeiro
authors.forename: Newton G
authors.initials: NG
authors.lastname: Castro
authors.forename: Ana Luisa P
authors.initials: AL
authors.lastname: Miranda
authors.forename: Eliezer J
authors.initials: EJ
authors.lastname: Barreiro
authors.forename: Carlos A M
authors.initials: CA
authors.lastname: Fraga
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D052117:Benzodioxoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D002351:Carrageenan / Q000737:chemistry; D003198:Computer Simulation; D018360:Crystallography, X-Ray; D016861:Cyclooxygenase Inhibitors / Q000378:metabolism; D004195:Disease Models, Animal; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy / Q000517:prevention & control; D005260:Female; D006835:Hydrazones / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013816:Thermodynamics
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D052117:Benzodioxoles; D016861:Cyclooxygenase Inhibitors; D006835:Hydrazones; C539858:N-(6-((2-benzylidenehydrazinyl)carbonyl)-1,3-benzodioxol-5-yl)methanesulfonamide; D002351:Carrageenan