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Design, synthesis and pharmacological evaluation of CVIB, a codrug of carvacrol and ibuprofen as a novel anti-inflammatory agent.
de Oliveira Pedrosa Rolim, Michelle; de Almeida, Anderson Rodrigues; da Rocha Pitta, Maira Galdino; de Melo Rêgo, Moacyr Jesus Barreto; Quintans-Júnior, Lucindo José; de Souza Siqueira Quintans, Jullyana; Heimfarth, Luana; Scotti, Luciana; Scotti, Marcus Tullius; da Cruz, Ryldene Marques Duarte; de Almeida, Reinaldo Nóbrega; da Silva, Teresinha Gonçalves; de Oliveira, Jonata Augusto; de Campos, Michel Leandro; Marchand, Pascal; Mendonça-Junior, Francisco Jaime Bezerra.
Afiliação
  • de Oliveira Pedrosa Rolim M; Laboratory of Synthesis and Drug Delivery, State University of Paraiba, João Pessoa, PB 58071-160, Brazil; Post-Graduation Program in Natural and Synthetic Bioactive Products, Federal University of Paraiba, João Pessoa, PB 58051-900, Brazil.
  • de Almeida AR; Laboratory of Immunomodulation and Novel Therapeutic Approaches, Federal University of Pernambuco, Recife, PE 50670-901, Brazil.
  • da Rocha Pitta MG; Laboratory of Immunomodulation and Novel Therapeutic Approaches, Federal University of Pernambuco, Recife, PE 50670-901, Brazil.
  • de Melo Rêgo MJB; Laboratory of Immunomodulation and Novel Therapeutic Approaches, Federal University of Pernambuco, Recife, PE 50670-901, Brazil.
  • Quintans-Júnior LJ; Laboratory of Neurosciences and Pharmacological Assays (LANEF) University of Sergipe, São Cristóvão, SE 49100-000, Brazil.
  • de Souza Siqueira Quintans J; Laboratory of Neurosciences and Pharmacological Assays (LANEF) University of Sergipe, São Cristóvão, SE 49100-000, Brazil.
  • Heimfarth L; Laboratory of Neurosciences and Pharmacological Assays (LANEF) University of Sergipe, São Cristóvão, SE 49100-000, Brazil.
  • Scotti L; Post-Graduation Program in Natural and Synthetic Bioactive Products, Federal University of Paraiba, João Pessoa, PB 58051-900, Brazil; Teaching and Research Management - University Hospital, Federal University of Paraiba, João Pessoa, PB 58051-900, Brazil.
  • Scotti MT; Post-Graduation Program in Natural and Synthetic Bioactive Products, Federal University of Paraiba, João Pessoa, PB 58051-900, Brazil.
  • da Cruz RMD; Post-Graduation Program in Natural and Synthetic Bioactive Products, Federal University of Paraiba, João Pessoa, PB 58051-900, Brazil.
  • de Almeida RN; Post-Graduation Program in Natural and Synthetic Bioactive Products, Federal University of Paraiba, João Pessoa, PB 58051-900, Brazil.
  • da Silva TG; Department of Antibiotics, Center for Biosciences, Federal University of Pernambuco, Recife, PE 50740-520, Brazil.
  • de Oliveira JA; Laboratory of Toxicology, São Paulo State University (UNESP), School of Pharmaceutical Sciences, Araraquara, SP 14801-902, Brazil.
  • de Campos ML; Health Research and Education Center (NUPADS), Federal University of Mato Grosso, Sinop, MT 78550-728, Brazil.
  • Marchand P; Université de Nantes, Cibles et Médicaments des Infections et du Cancer, IICiMed, EA 1155, F-44000 Nantes, France.
  • Mendonça-Junior FJB; Laboratory of Synthesis and Drug Delivery, State University of Paraiba, João Pessoa, PB 58071-160, Brazil; Post-Graduation Program in Natural and Synthetic Bioactive Products, Federal University of Paraiba, João Pessoa, PB 58051-900, Brazil. Electronic address: franciscojaime@uepb.edu.br.
Int Immunopharmacol ; 76: 105856, 2019 Nov.
Article em En | MEDLINE | ID: mdl-31480005
The search for new drugs with anti-inflammatory properties remains a challenge for modern medicine. Among the various strategies for drug discovery, deriving new chemical entities from known bioactive natural and/or synthetic compounds remains a promising approach. Here, we designed and synthesized CVIB, a codrug developed by association of carvacrol (a phenolic monoterpene) with ibuprofen (a non-steroidal anti-inflammatory drug). In silico pharmacokinetic and physicochemical properties evaluation indicated low aqueous solubility (LogP ≥5.0). Nevertheless, the hybrid presented excellent oral bioavailability, gastrointestinal tract absorption, and low toxicity. CVIB did not present cytotoxicity in peripheral blood mononuclear cells (PBMCs), and promoted a significant reduction in IL-2, IL-10, IL-17, and IFN-γ cytokine levels in vitro. The LD50 was estimated to be approximately 5000 mg/kg. CVIB was stable and detectable in human plasma after 24 h. In vivo anti-inflammatory evaluations revealed that CVIB at 10 and 50 mg/kg i.p. caused a significant decrease in total leukocyte count (p < 0.01) and provoked a significant reduction in IL-1ß (p < 0.01). CVIB at 10 mg/kg i.p. efficiently decreased inflammatory parameters better than the physical mixture (carvacrol + ibuprofen 10 mg/kg i.p.). The results suggest that the codrug approach is a good option for drug design and development, creating the possibility of combining NSAIDs with natural products in order to obtain new hybrid drugs may be useful for treatment of inflammatory diseases.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Ibuprofeno / Cimenos / Anti-Inflamatórios Limite: Animals / Humans / Male Idioma: En Revista: Int Immunopharmacol Assunto da revista: ALERGIA E IMUNOLOGIA / FARMACOLOGIA Ano de publicação: 2019 Tipo de documento: Article País de afiliação: Brasil País de publicação: Holanda
Texto completo
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Ibuprofeno / Cimenos / Anti-Inflamatórios Limite: Animals / Humans / Male Idioma: En Revista: Int Immunopharmacol Assunto da revista: ALERGIA E IMUNOLOGIA / FARMACOLOGIA Ano de publicação: 2019 Tipo de documento: Article País de afiliação: Brasil País de publicação: Holanda