Molecules 2014, 19, 20197-20226; doi:10.3390/molecules191220197 OPEN ACCESS molecules ISSN 1420-3049 www.mdpi.com/journal/molecules Article Multitarget Molecular Hybrids of Cinnamic Acids Aikaterini Peperidou 1, Dorothea Kapoukranidou 2, Christos Kontogiorgis 3 and Dimitra Hadjipavlou-Litina 1,* 1 Department of Pharmaceutical Chemistry, School of Pharmacy, Faculty of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki 54124, Greece; E-Mail:
[email protected] 2 Department of Physiology, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki 54124, Greece; E-Mail:
[email protected] 3 Laboratory of Hygiene and Environmental Protection, Medical School, Democritus University of Thrace, Dragana (Campus), Alexandroupolis 68100, Greece; E-Mail:
[email protected] * Author to whom correspondence should be addressed; E-Mail:
[email protected]; Tel.: +30-231-099-7627; Fax: +30-231-099-7679. External Editor: Derek J. McPhee Received: 27 October 2014; in revised form: 14 November 2014 / Accepted: 25 November 2014 / Published: 2 December 2014 Abstract: 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—2e, 2a, 2g—and 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 μΜ and 98.1%, whereas the hybrid 3b of bromobenzyloxycinnamic acid and hymechromone exhibited simultaneously good LOX inhibitory activity (IC50 = 50 μΜ) and the highest anti-proteolytic activity (IC50= 5 μΜ). 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.