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https://hdl.handle.net/1822/64442
Título: | Biological evaluation of naproxen–dehydrodipeptide conjugates with self-hydrogelation capacity as dual LOX/COX inhibitors |
Autor(es): | Moreira, Rute Jervis, Peter John Carvalho, André Ferreira, Paula M. T. Martins, J. A. R. Valentão, Patrícia Andrade, Paula B. Pereira, David M. |
Palavras-chave: | anti-inflammatory hydrogel dehydrodipeptide cyclooxygenase lipoxygenase cancer proteasome |
Data: | 3-Fev-2020 |
Editora: | Multidisciplinary Digital Publishing Institute |
Revista: | Pharmaceutics |
Citação: | Moreira, R.; Jervis, P.J.; Carvalho, A.; Ferreira, P.M.T.; Martins, J.A.; Valentão, P.; Andrade, P.B.; Pereira, D.M. Biological Evaluation of Naproxen–Dehydrodipeptide Conjugates with Self-Hydrogelation Capacity as Dual LOX/COX Inhibitors. Pharmaceutics 2020, 12, 122. |
Resumo(s): | The use of peptide–drug conjugates is emerging as a powerful strategy for targeted drug delivery. Previously, we have found that peptides conjugated to a non-steroidal anti-inflammatory drug (NSAID), more specifically naproxen–dehydrodipeptide conjugates, readily form nanostructured fibrilar supramolecular hydrogels. These hydrogels were revealed as efficacious nano-carriers for drug delivery applications. Moreover, the incorporation of superparamagnetic iron oxide nanoparticles (SPIONs) rendered the hydrogels responsive to external magnetic fields, undergoing gel-to-solution phase transition upon remote magnetic excitation. Thus, magnetic dehydrodipeptide-based hydrogels may find interesting applications as responsive Magnetic Resonance Imaging (MRI) contrast agents and for magnetic hyperthermia-triggered drug-release applications. Supramolecular hydrogels where the hydrogelator molecule is endowed with intrinsic pharmacological properties can potentially fulfill a dual function in drug delivery systems as (passive) nanocariers for incorporated drugs and as active drugs themselves. In this present study, we investigated the pharmacological activities of a panel of naproxen–dehydrodipeptide conjugates, previously studied for their hydrogelation ability and as nanocarriers for drug-delivery applications. A focused library of dehydrodipeptides, containing <i>N</i>-terminal canonical amino acids (Phe, Tyr, Trp, Ala, Asp, Lys, Met) <i>N</i>-capped with naproxen and linked to a <i>C</i>-terminal dehydroaminoacid (ΔPhe, ΔAbu), were evaluated for their anti-inflammatory and anti-cancer activities, as well as for their cytotoxicity to non-cancer cells, using a variety of enzymatic and cellular assays. All compounds except one were able to significantly inhibit lipoxygenase (LOX) enzyme at a similar level to naproxen. One of the compounds <b>4</b> was able to inhibit the cyclooxygenase-2 (COX-2) to a greater extent than naproxen, without inhibiting cyclooxygenase-1 (COX-1), and therefore is a potential lead in the search for selective COX-2 inhibitors. This hydrogelator is a potential candidate for dual COX/LOX inhibition as an optimised strategy for treating inflammatory conditions. |
Tipo: | Artigo |
URI: | https://hdl.handle.net/1822/64442 |
DOI: | 10.3390/pharmaceutics12020122 |
e-ISSN: | 1999-4923 |
Versão da editora: | https://www.mdpi.com/1999-4923/12/2/122 |
Arbitragem científica: | yes |
Acesso: | Acesso aberto |
Aparece nas coleções: | CDQuim - Artigos (Papers) |
Ficheiros deste registo:
Ficheiro | Descrição | Tamanho | Formato | |
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pharmaceutics-12-00122-v2.pdf | 4,04 MB | Adobe PDF | Ver/Abrir |
Este trabalho está licenciado sob uma Licença Creative Commons