Cinnamate Hybrids: A Unique Family of Compounds with Multiple Biological Activities

Cinnamic acid derivatives are widely distributed in nature presenting a wide range of biological activities: antiseptic, stimulant, carminative and insecticidal activities. Hydroxy- cinnamic acids, especially caffeic, ferulic and chlorogenic, present various biological activities and they are synthesized in nature through the phenylpropanoid pathway. Additionally, the cinnamoyl moiety is present in various drugs such as a) Ozagrel, an imidazole π - substituted cinnamic acid acting as a thromboxane A2 synthase inhibitor, used therapeutically for treating acute ischemic stroke, b) Cinnarizine, Cinanserin and Tranilast, a series of antiallergic agents etc. During the last decade, scientists have focused on multifunctional molecules instead of a single molecule hitting one target. Multi-target drugs can be beneficial for the treatment of complex and multifunctional diseases. A variety of multi-target drugs contain the cinnamic acid moiety due to its biological importance and combination of biological activities e.g. antioxidant, antiiflammatory, anticancer, antituberculosis, antifungal, antimalarial, antiatherogenic, antimicrobial activities. Recently for the treatment of complex diseases hybrid drugs combining two pharmaceutical moieties in one molecule have been developed. These molecules are more medically effective than their individual components. In this review, a survey of cinnamate hybrids, that is molecules that combine the cinnamic acid moiety with at least a second pharmacophore with or without a linker, acting as "multi-target" agents, is given. The hybrids are listed in terms of their biological activity and applications as anti-Alzheimer, anticancer agents as well as for cardiovascular diseases, as antivirals, antimalarials etc.