Salicytamide: a New Anti-inflammatory Designed Drug Candidate.

Autor: Guedes KMM; Programa de Pós-Graduação em Ciências Farmacêuticas, Instituto de Ciências da Saúde, Health Science Institute, Federal University of Pará, Belem, Pará, 66075-900, Brazil., Borges RS; Pharmaceutic Chemical Laboratory, Health Science Institute, Federal University of Pará, Belem, Pará, 66075-900, Brazil., Fontes-Júnior EA; Programa de Pós-Graduação em Ciências Farmacêuticas, Instituto de Ciências da Saúde, Health Science Institute, Federal University of Pará, Belem, Pará, 66075-900, Brazil.; Laboratory of Inflammation and Behaviour Pharmacology, Health Science Institute, Federal University of Pará, Belem, Pará, 66075-900, Brazil., Silva ASB; Programa de Pós-Graduação em Ciências Farmacêuticas, Instituto de Ciências da Saúde, Health Science Institute, Federal University of Pará, Belem, Pará, 66075-900, Brazil., Fernandes LMP; Laboratory of Inflammation and Behaviour Pharmacology, Health Science Institute, Federal University of Pará, Belem, Pará, 66075-900, Brazil., Cartágenes SC; Laboratory of Inflammation and Behaviour Pharmacology, Health Science Institute, Federal University of Pará, Belem, Pará, 66075-900, Brazil., Pinto ACG; Laboratory of Toxicology, Health Science Institute, Federal University of Pará, Belem, Pará, 66075-900, Brazil., Silva ML; Laboratory of Inflammation and Behaviour Pharmacology, Health Science Institute, Federal University of Pará, Belem, Pará, 66075-900, Brazil., Queiroz LMD; Programa de Pós-Graduação em Ciências Farmacêuticas, Instituto de Ciências da Saúde, Health Science Institute, Federal University of Pará, Belem, Pará, 66075-900, Brazil., Vieira JLF; Programa de Pós-Graduação em Ciências Farmacêuticas, Instituto de Ciências da Saúde, Health Science Institute, Federal University of Pará, Belem, Pará, 66075-900, Brazil., Sousa PJC; Laboratory of Inflammation and Behaviour Pharmacology, Health Science Institute, Federal University of Pará, Belem, Pará, 66075-900, Brazil., Maia CSF; Programa de Pós-Graduação em Ciências Farmacêuticas, Instituto de Ciências da Saúde, Health Science Institute, Federal University of Pará, Belem, Pará, 66075-900, Brazil. crismaia@ufpa.br.; Laboratory of Inflammation and Behaviour Pharmacology, Health Science Institute, Federal University of Pará, Belem, Pará, 66075-900, Brazil. crismaia@ufpa.br.
Jazyk: angličtina
Zdroj: Inflammation [Inflammation] 2018 Aug; Vol. 41 (4), pp. 1349-1360.
DOI: 10.1007/s10753-018-0783-x
Abstrakt: Salicytamide is a new drug developed through molecular modelling and rational drug design by the molecular association of paracetamol and salicylic acid. This study was conducted to assess the acute oral toxicity, antinociceptive, and antioedematogenic properties of salicytamide. Acute toxicity was based on the OECD 423 guidelines. Antinociceptive properties were investigated using the writhing, hot plate and formalin tests in Swiss mice. Antioedematogenic properties were evaluated using the carrageenan-induced paw oedema model and croton oil-induced dermatitis in Wistar rats. Salicytamide did not promote behavioural changes or animal deaths during acute oral toxicity evaluation. Furthermore, salicytamide exhibited peripheral antinociceptive activity as evidenced by the reduction in writhing behaviour (ED50 = 4.95 mg/kg) and licking time in the formalin test's inflammatory phase. Also, salicytamide elicited central antinociceptive activity on both hot plate test and formalin test's neurogenic phase. Additionally, salicytamide was effective in reducing carrageenan or croton oil-induced oedema formation. Overall, we have shown that salicytamide, proposed here as a new NSAID candidate, did not induce oral acute toxicity and elicited both peripheral antinociceptive effects (about 10-25 times more potent than its precursors in the writhing test) and antioedematogenic properties. Salicytamide also presented central antinociceptive activity, which seems to be mediated through opioid-independent mechanisms. These findings reveal salicytamide as a promising antinociceptive/antioedematogenic drug candidate.
Databáze: MEDLINE
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