Synthesis of novel trans-stilbene derivatives and evaluation of their potent antioxidant and neuroprotective effects

• Published in: European journal of medicinal chemistry 2009-08, Vol.44 (8), p.3166-3174
• Main Authors: Jung, Jae-Chul, Lim, Eunyoung, Lee, Yongnam, Kang, Jun-Mo, Kim, Heejeong, Jang, Soyong, Oh, Seikwan, Jung, Mankil
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Bones, joints and connective tissue. Antiinflammatory agents; Cell Line; Cerebral Cortex - cytology; Drug Design; Free Radical Scavengers - chemical synthesis; Free Radical Scavengers - chemistry; Free Radical Scavengers - pharmacology; Free radical-scavenging effects; Kinetics; L-Lactate Dehydrogenase - metabolism; LPS-induced NO generation; Medical sciences; Mice; Mice, Inbred ICR; Microglia - cytology; Microglia - drug effects; Microglia - metabolism; Neurons - drug effects; Neurons - metabolism; Neuropharmacology; Neuroprotective activity; Neuroprotective agent; Neuroprotective Agents - chemical synthesis; Neuroprotective Agents - chemistry; Neuroprotective Agents - pharmacology; Nitric Oxide - metabolism; Pharmacology. Drug treatments; Stereoisomerism; Stilbenes - chemical synthesis; Stilbenes - chemistry; Stilbenes - pharmacology; trans-Stilbene derivatives; Wittig–Horner reaction
• ISSN: 0223-5234; 1768-3254
• DOI: 10.1016/j.ejmech.2009.03.011

A convenient synthesis and the biological properties of new amides, esters and other derivatives of trans-stilbene are described. The key synthetic strategies involve the Wittig–Horner reaction of a phosphonium salt 9 and an aldehyde 10 to generate ( E)- or ( Z)-olefins and a coupling reaction of an acid 12 and various amines 13a– n to give trans-stilbene derivatives 15a– n in high yields. A amide derivative 15g showed three times more in vitro free radical-scavenging activity than resveratrol, while another 15d exhibited strong inhibitory activity against lipopolysaccharide (LPS) a-induced NO generation. Allylamide analogue 15a showed the most potent neuroprotective activity in glutamate-induced primary cortical neuron cells. [Display omitted] trans-Stilbene allylamide showed the most potent protective activity against glutamate-induced neurotoxicity and inhibiting the nitrite production.