{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,25]],"date-time":"2026-04-25T04:40:18Z","timestamp":1777092018329,"version":"3.51.4"},"reference-count":45,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2020,2,3]],"date-time":"2020-02-03T00:00:00Z","timestamp":1580688000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["under the Project PTDC\/QUI-QOR\/29015\/2017 and CQ\/UM UID\/QUI\/00686\/2013 and UID\/QUI\/0686\/2016. The NMR spectrometers are part of the National NMR Network (PTNMR) and are partially supported by Infrastructure Project No 022161 (co-financed by FEDER through"],"award-info":[{"award-number":["under the Project PTDC\/QUI-QOR\/29015\/2017 and CQ\/UM UID\/QUI\/00686\/2013 and UID\/QUI\/0686\/2016. The NMR spectrometers are part of the National NMR Network (PTNMR) and are partially supported by Infrastructure Project No 022161 (co-financed by FEDER through"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["This work is funded by FEDER funds through the COMPETE 2020 Programme and National Funds through FCT-Portuguese Foundation for Science and Technology under the Project UID\/CTM\/50025\/2013."],"award-info":[{"award-number":["This work is funded by FEDER funds through the COMPETE 2020 Programme and National Funds through FCT-Portuguese Foundation for Science and Technology under the Project UID\/CTM\/50025\/2013."]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>The use of peptide\u2013drug 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\u2013dehydrodipeptide 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\u2013dehydrodipeptide conjugates, previously studied for their hydrogelation ability and as nanocarriers for drug-delivery applications. A focused library of dehydrodipeptides, containing N-terminal canonical amino acids (Phe, Tyr, Trp, Ala, Asp, Lys, Met) N-capped with naproxen and linked to a C-terminal dehydroaminoacid (\u0394Phe, \u0394Abu), 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 4 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.<\/jats:p>","DOI":"10.3390\/pharmaceutics12020122","type":"journal-article","created":{"date-parts":[[2020,2,6]],"date-time":"2020-02-06T02:59:18Z","timestamp":1580957958000},"page":"122","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Biological Evaluation of Naproxen\u2013Dehydrodipeptide Conjugates with Self-Hydrogelation Capacity as Dual LOX\/COX Inhibitors"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6964-8110","authenticated-orcid":false,"given":"Rute","family":"Moreira","sequence":"first","affiliation":[{"name":"REQUIMTE\/LAQV, Laborat\u00f3rio de Farmacognosia, Departamento de Qu\u00edmica, Faculdade de Farm\u00e1cia, Universidade do Porto, R. Jorge Viterbo Ferreira, n 228, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5550-4535","authenticated-orcid":false,"given":"Peter J.","family":"Jervis","sequence":"additional","affiliation":[{"name":"Centre of Chemistry, University of Minho, Campus de Gualtar, 4710-057 Braga, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4816-6371","authenticated-orcid":false,"given":"Andr\u00e9","family":"Carvalho","sequence":"additional","affiliation":[{"name":"Centre of Chemistry, University of Minho, Campus de Gualtar, 4710-057 Braga, Portugal"}]},{"given":"Paula M. T.","family":"Ferreira","sequence":"additional","affiliation":[{"name":"Centre of Chemistry, University of Minho, Campus de Gualtar, 4710-057 Braga, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9323-3978","authenticated-orcid":false,"given":"Jos\u00e9 A.","family":"Martins","sequence":"additional","affiliation":[{"name":"Centre of Chemistry, University of Minho, Campus de Gualtar, 4710-057 Braga, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0740-4396","authenticated-orcid":false,"given":"Patr\u00edcia","family":"Valent\u00e3o","sequence":"additional","affiliation":[{"name":"REQUIMTE\/LAQV, Laborat\u00f3rio de Farmacognosia, Departamento de Qu\u00edmica, Faculdade de Farm\u00e1cia, Universidade do Porto, R. Jorge Viterbo Ferreira, n 228, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9764-3920","authenticated-orcid":false,"given":"Paula B.","family":"Andrade","sequence":"additional","affiliation":[{"name":"REQUIMTE\/LAQV, Laborat\u00f3rio de Farmacognosia, Departamento de Qu\u00edmica, Faculdade de Farm\u00e1cia, Universidade do Porto, R. Jorge Viterbo Ferreira, n 228, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0384-7592","authenticated-orcid":false,"given":"David M.","family":"Pereira","sequence":"additional","affiliation":[{"name":"REQUIMTE\/LAQV, Laborat\u00f3rio de Farmacognosia, Departamento de Qu\u00edmica, Faculdade de Farm\u00e1cia, Universidade do Porto, R. Jorge Viterbo Ferreira, n 228, 4050-313 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2020,2,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1038\/nrd4333","article-title":"Multifunctional, stimuli-sensitive nanoparticulate systems for drug delivery","volume":"13","author":"Torchilin","year":"2014","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1038\/nrd1632","article-title":"Recent advances with liposomes as pharmaceutical carriers","volume":"4","author":"Torchilin","year":"2005","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1016\/j.addr.2012.09.033","article-title":"Nanoparticle and targeted systems for cancer therapy","volume":"64","author":"Blanchette","year":"2012","journal-title":"Adv. Drug Deliv. 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