Synthesis and evaluation of neuroprotective alpha,beta-unsaturated aldehyde scavenger histidyl-containing analogues of carnosine.
The synthesis, scavenging activity, and cytoprotective profiles of histidyl-containing carnosine analogues bearing hydrazide or 1,2-diol moieties is reported. Some compounds have demonstrated higher aldehyde-sequestering efficiency than carnosine and were also efficient in protecting SH-SY5Y neuroblastoma cells and rat hippocampal neurons from 4-hydroxy-trans-2,3-nonenal (HNE)-mediated death. The cytoprotective efficacy of these compounds suggests their potential use as therapeutic agents for disorders that involve excessive membrane lipids peroxidation and HNE-mediated neuronal toxicity.
Guiotto
Andrea
A
Institute of Biomolecular Chemistry of CNR, Padova Unit, via F. Marzolo, 1, 35131 Padova, Italy. andrea.guiotto@unipd.it
Calderan
Andrea
A
Ruzza
Paolo
P
Osler
Alessio
A
Rubini
Chiara
C
Jo
Dong-Gyu
DG
Mattson
Mark P
MP
Borin
Gianfranco
G
D000447:Aldehydes / Q000378:metabolism / Q000633:toxicity*; D000818:Animals; D002336:Carnosine / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D019610:Cytoprotection; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects; D006639:Histidine / Q000737:chemistry*; D006801:Humans; D009474:Neurons / Q000166:cytology / Q000187:drug effects; D018696:Neuroprotective Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D013329:Structure-Activity Relationship
D000447:Aldehydes; D018696:Neuroprotective Agents; D006639:Histidine; D002336:Carnosine; C027576:4-hydroxy-2-nonenal