{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,13]],"date-time":"2025-12-13T07:07:28Z","timestamp":1765609648464,"version":"build-2065373602"},"reference-count":60,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2014,12,2]],"date-time":"2014-12-02T00:00:00Z","timestamp":1417478400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Research Committee of Aristotle University of Thessaloniki, Thessaloniki, Greece","award":["89321"],"award-info":[{"award-number":["89321"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>In an attempt to synthesize potential new multitarget agents, 11 novel hybrids incorporating cinnamic acids and paracetamol, 4-\/7-hydroxycoumarin, benzocaine,  p-aminophenol and m-aminophenol were synthesized. Three hybrids\u20142e, 2a, 2g\u2014and 3b were found to be multifunctional agents. The hybrid 2e derived from the phenoxyphenyl cinnamic acid and m-acetamidophenol showed the highest lipoxygenase (LOX) inhibition and analgesic activity (IC50 = 0.34 \u03bc\u039c and 98.1%, whereas the hybrid 3b of bromobenzyloxycinnamic acid and hymechromone exhibited simultaneously good LOX inhibitory activity (IC50 = 50 \u03bc\u039c) and the highest anti-proteolytic activity (IC50= 5 \u03bc\u039c). The hybrid 2a of phenyloxyphenyl acid with paracetamol showed a high analgesic activity (91%) and appears to be a promising agent for treating peripheral nerve injuries. Hybrid 2g which has an ester and an amide bond presents an interesting combination of anti-LOX and anti-proteolytic activity. The esters were found very potent and especially those derived from paracetamol and m-acetamidophenol. The amides follow. Based on 2D-structure\u2013activity relationships it was observed that both steric and electronic parameters play major roles in the activity of these compounds. Molecular docking studies point to the fact that allosteric interactions might govern the LOX-inhibitor binding.<\/jats:p>","DOI":"10.3390\/molecules191220197","type":"journal-article","created":{"date-parts":[[2014,12,2]],"date-time":"2014-12-02T10:57:54Z","timestamp":1417517874000},"page":"20197-20226","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Multitarget Molecular Hybrids of Cinnamic Acids"],"prefix":"10.3390","volume":"19","author":[{"given":"Aikaterini","family":"Peperidou","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Chemistry, School of Pharmacy, Faculty of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki 54124, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dorothea","family":"Kapoukranidou","sequence":"additional","affiliation":[{"name":"Department of Physiology, School of Medicine, Faculty of Health Sciences,  Aristotle University of Thessaloniki, Thessaloniki 54124, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christos","family":"Kontogiorgis","sequence":"additional","affiliation":[{"name":"Laboratory of Hygiene and Environmental Protection, Medical School, Democritus University of Thrace, Dragana (Campus), Alexandroupolis 68100, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dimitra","family":"Hadjipavlou-Litina","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, School of Pharmacy, Faculty of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki 54124, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2014,12,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"749","DOI":"10.2174\/138955712801264792","article-title":"Antioxidant and antimicrobial activities of cinnamic acid derivatives","volume":"12","author":"Sova","year":"2012","journal-title":"Mini Rev. 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