Premium
Discovery of neurotrophic agents based on hydroxycinnamic acid scaffold
Author(s) -
Hosseini Razieh,
Moosavi Fatemeh,
Rajaian Hamid,
Silva Tiago,
Magalhães e Silva Diogo,
Soares Pedro,
Saso Luciano,
Edraki Najmeh,
Miri Ramin,
Borges Fernanda,
Firuzi Omidreza
Publication year - 2016
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/cbdd.12829
Subject(s) - scaffold , chemistry , neurotrophin , hydroxycinnamic acid , neuroscience , biochemistry , biology , computer science , programming language , receptor , antioxidant
The number of people affected by neurodegenerative disorders such as Alzheimer's disease and Parkinson's disease is rapidly increasing owing to the global increase in life expectancy. Small molecules with neurotrophic effects have great potential for management of these neurological disorders. In this study, different (C1–C12) alkyl ester derivatives of hydroxycinnamic acids ( HCA s) were synthesized (a total of 30 compounds). The neurotrophic capacity of the test compounds was examined by measuring promotion of survival in serum‐deprived conditions and enhancement of nerve growth factor ( NGF )‐induced neurite outgrowth in PC 12 neuronal cells. p ‐Coumaric, ferulic, and sinapic acids and their esters did not alter cell survival, while caffeic acid and all its alkyl esters, especially decyl and dodecyl caffeate, significantly promoted neuronal survival at 25 μ m . Methyl, ethyl, propyl, and butyl caffeate esters also significantly enhanced NGF ‐induced neurite outgrowth, among which the most effective ones were propyl and butyl esters, which at 5 μ m led to 25‐ and 22‐fold increases in the number of neurites, respectively. The findings of the docking study suggested phosphatidylinositol 3‐kinase ( PI 3K) as the potential molecular target. In conclusion, our findings demonstrate that alkyl esters of caffeic acid can be useful as scaffolds for the discovery of therapeutic agents for neurodegenerative diseases.