Design, synthesis and pharmacological evaluation of CVIB, a codrug of carvacrol and ibuprofen as a novel anti-inflammatory agent.

Design, synthesis and pharmacological evaluation of CVIB, a codrug of carvacrol and ibuprofen as a novel anti-inflammatory agent.
Int Immunopharmacol. 2019 Aug 31;76:105856
Authors: de Oliveira Pedrosa Rolim M, de Almeida AR, da Rocha Pitta MG, de Melo Rêgo MJB, Quintans-Júnior LJ, de Souza Siqueira Quintans J, Heimfarth L, Scotti L, Scotti MT, da Cruz RMD, de Almeida RN, da Silva TG, de Oliveira JA, de Campos ML, Marchand P, Mendonça-Junior FJB
Abstract
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 ev...

Source: International Immunopharmacology - August 30, 2019 Category: Allergy & Immunology Authors: de Oliveira Pedrosa Rolim M, de Almeida AR, da Rocha Pitta MG, de Melo Rêgo MJB, Quintans-Júnior LJ, de Souza Siqueira Quintans J, Heimfarth L, Scotti L, Scotti MT, da Cruz RMD, de Almeida RN, da Silva TG, de Oliveira JA, de Campos ML, Marchand P, Mendo Tags: Int Immunopharmacol Source Type: research