title: Sulphonamide and sulphonyl-hydrazone cyclic imide derivatives: antinociceptive activity, molecular modeling and in silico ADMET screening.
abstract: In this paper, we describe the antinociceptive activity, molecular modeling and in silico ADMET screening of a series of sulphonyl-hydrazone and sulphonamide imidobenzene derivatives. Among these compounds, the sulphonyl-hydrazones 9 and 11 showed the most potent analgesic activity (ID(50) = 5.1 and 6.8 μmol/kg, respectively). Interestingly, all derivatives evaluated in this study have a better analgesic profile than the control drugs, acetyl salicylic acid and acetaminophen. Derivative 9 was the most promising compound; with a level of activity that was 24 times higher than the control drugs. Our SAR study showed a relationship among the distribution of the frontier orbital HOMO coefficients, HOMO-LUMO energy gap of these molecules and their reactivity. The best analgesic compounds (including 6, 9, 10, 11 and 12) fulfilled the Lipinski "rule-of-five", which is theoretically important for good drug absorption and permeation.
authors.affiliation: Departamento de Química, Universidade Federal de Santa Catarina, Florianópolis, Brazil.
authors.forename: Kely N
authors.initials: KN
authors.lastname: de Oliveira
authors.forename: Márcia M
authors.initials: MM
authors.lastname: Souza
authors.forename: Plínio Cunha
authors.initials: PC
authors.lastname: Sathler
authors.forename: Uiaran O
authors.initials: UO
authors.lastname: Magalhães
authors.forename: Carlos R
authors.initials: CR
authors.lastname: Rodrigues
authors.forename: Helena C
authors.initials: HC
authors.lastname: Castro
authors.forename: Patrícia R
authors.initials: PR
authors.lastname: Palm
authors.forename: Maicon
authors.initials: M
authors.lastname: Sarda
authors.forename: Pablo E
authors.initials: PE
authors.lastname: Perotto
authors.forename: Sabrina
authors.initials: S
authors.lastname: Cezar
authors.forename: Monique A
authors.initials: MA
authors.lastname: de Brito
authors.forename: Ariane S S R
authors.initials: AS
authors.lastname: Ferreira
authors.forename: Lúcio Mendes
authors.initials: LM
authors.lastname: Cabral
authors.forename: Clodoaldo
authors.initials: C
authors.lastname: Machado
authors.forename: Ricardo J
authors.initials: RJ
authors.lastname: Nunes
mesh_terms: D000700:Analgesics / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D004195:Disease Models, Animal; D015195:Drug Design; D006835:Hydrazones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D006860:Hydrogen Bonding; D057927:Hydrophobic and Hydrophilic Interactions; D007094:Imides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D051379:Mice; D008958:Models, Molecular; D015394:Molecular Structure; D010146:Pain / Q000188:drug therapy; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D000700:Analgesics; D006835:Hydrazones; D007094:Imides; D013449:Sulfonamides