Synthesis of novel trans-stilbene derivatives and evaluation of their potent antioxidant and neuroprotective effects.
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.
Jung
Jae-Chul
JC
Department of Neuroscience and Medical Research Institute, School of Medicine, Ewha Womans University, Seoul, Republic of Korea.
Lim
Eunyoung
E
Lee
Yongnam
Y
Kang
Jun-Mo
JM
Kim
Heejeong
H
Jang
Soyong
S
Oh
Seikwan
S
Jung
Mankil
M
D000818:Animals; D002460:Cell Line; D002540:Cerebral Cortex / Q000166:cytology; D015195:Drug Design; D016166:Free Radical Scavengers / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D007700:Kinetics; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D051379:Mice; D008813:Mice, Inbred ICR; D017628:Microglia / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D018696:Neuroprotective Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism; D013237:Stereoisomerism; D013267:Stilbenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
D016166:Free Radical Scavengers; D018696:Neuroprotective Agents; D013267:Stilbenes; D009569:Nitric Oxide; D007770:L-Lactate Dehydrogenase