Author | Moreira, Diogo Rodrigo Magalhaes | |
Author | Santos, Dourivaldo Silva | |
Author | Espírito Santo, Renan Fernandes do | |
Author | Santos, Flávia Evangelista Dos | |
Author | Oliveira Filho, Gevanio Bezerra de | |
Author | Leite, Ana Cristina Lima | |
Author | Soares, Milena Botelho Pereira | |
Author | Villarreal, Cristiane Flora | |
Access date | 2018-03-26T14:02:21Z | |
Available date | 2018-03-26T14:02:21Z | |
Document date | 2017 | |
Citation | MOREIRA, D. R. M. et al. Structural improvement of new thiazolidinones compounds with antinociceptive activity in experimental chemotherapy-induced painful neuropathy. Chemical Biology and Drug Design, v. 90, p. 297–307, 2017. | pt_BR |
ISSN | 1747-0277 | pt_BR |
URI | https://www.arca.fiocruz.br/handle/icict/25491 | |
Sponsorship | FAPESB, Grant/Award Number: PNX 0009/2009 and RED0010/2012. | pt_BR |
Language | eng | pt_BR |
Publisher | Wiley | pt_BR |
Rights | open access | pt_BR |
Subject in Portuguese | Analgésico | pt_BR |
Subject in Portuguese | Glitazonas | pt_BR |
Subject in Portuguese | Dor neuropática | pt_BR |
Subject in Portuguese | Oxaliplatina | pt_BR |
Subject in Portuguese | PPAR | pt_BR |
Title | Structural improvement of new thiazolidinones compounds with antinociceptive activity in experimental chemotherapy-induced painful neuropathy | pt_BR |
Type | Article | pt_BR |
DOI | 10.1111/cbdd.12951 | |
Abstract | Chemotherapy-induced neuropathy is a disabling pain condition resulting from chemotherapy for cancers. Up to now, no drug is available to cure chemotherapy-induced neuropathy. In the present study, we describe the structural design, synthesis, chemical and pharmacological characterization of 15 thiazolidinones, a class of potential analgesic compounds. The synthesis of new thiazolidinones was achieved by using the thiazolidinone heterocyclic as main structural pharmacophoric group and varying the substituents attached to the phenyl near to the iminic bond. The analgesic potential of the compounds was investigated in a mice model of oxaliplatin-induced neuropathic pain, using von Frey, rota-rod and open-field tests. Except for compound 14, these thiazolidinones exhibited antinociceptive property without causing motor impairment. Thiazolidinones 12, 15 and 16 displayed a dose-dependent antinociceptive effect, with similar efficacy and enhanced potency than gabapentin, the gold standard drug used for neuropathic pain. In addition, the antinociceptive activity of 16 lasted longer than gabapentin. The antinociceptive effect of thiazolidinones was prevented by GW9662, a PPARγ antagonist. The main antinociceptive compounds exhibited positive Lipinski's index, predicting their oral bioavailability. In conclusion, the structural design performed here led to the identification of new compounds endowed with potent antinociceptive activity, potentially useful to treat chemotherapy-induced neuropathic pain. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil | pt_BR |
Affilliation | Universidade Federal da Bahia. Faculdade de Farmácia. Salvador, BA, Brasil | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Faculdade de Farmácia. Salvador, BA, Brasil | pt_BR |
Affilliation | Universidade Federal da Bahia. Faculdade de Farmácia. Salvador, BA, Brasil | pt_BR |
Affilliation | Universidade Federal de Pernambuco. Centro de Ciências da Saúde. Departamento de Ciências Farmacêuticas. Recife, PE, Brazil | pt_BR |
Affilliation | Universidade Federal de Pernambuco. Centro de Ciências da Saúde. Departamento de Ciências Farmacêuticas. Recife, PE, Brazil | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / Hospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, Brasil | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Faculdade de Farmácia. Salvador, BA, Brasil | pt_BR |
Subject | Analgesic | pt_BR |
Subject | Glitazones | pt_BR |
Subject | Neuropathic pain | pt_BR |
Subject | Oxaliplatin | pt_BR |
Subject | PPAR | pt_BR |