RT Journal Article
T1 Insights into the Discovery of Novel Neuroprotective Agents: A Comparative Study between Sulfanylcinnamic Acid Derivatives and Related Phenolic Analogues
A1 Chavarria, Daniel
A1 Fernandes, Carlos
A1 Aguiar, Brandon
A1 Silva, Tiago
A1 Garrido, Jorge
A1 Remião, Fernando
A1 Oliveira, Paulo J.
A1 Uriarte Villares, Eugenio
A1 Borges, Fernanda
K1 Cinnamic acid
K1 4-thioferulic acid derivatives
K1 Ferulic acid derivatives
K1 Antioxidant activity
K1 Cytotoxicity
K1 Neuroprotection
AB Exogenous antioxidants may be beneficial therapeutic tools to tackle the oxidative damage in neurodegenerative diseases by regulation of the redox state that is critical for cell viability and organ function. Inspired by natural plant polyphenols, a series of cinnamic acid-based thiophenolic and phenolic compounds were synthesized and their antioxidant and neuroprotective properties were studied. In general, our results showed that the replacement of the hydroxyl group (OH) by a sulfhydryl group (SH) increased the radical scavenging activity and enhanced the reaction rate with 1,1-diphenyl-2-picrylhydrazyl radical (DPPH•) and galvinoxyl radical (GO•). These results correlated well with the lower oxidation potential (Ep) values of thiophenols. However, a lower peroxyl radical (ROO•) scavenging activity was observed for thiophenols in oxygen radical absorbance capacity (ORAC-FL) assay. Furthermore, the introduction of 5-methoxy and 5-phenyl groups in the aromatic ring of 4-thioferulic acid (TFA) 2 and ferulic acid (FA) 1 did not significantly improve their antioxidant activity, despite the slight decrease of Ep observed for compounds 5, 6, and 9. Concerning cinnamic acid amides, the antioxidant profile was similar to the parent compounds. None of the compounds under study presented significant cytotoxic effects in human differentiated neuroblastoma cells. Thiophenolic amide 3 stands out as the most promising thiophenol-based antioxidant, showing cellular neuroprotective effects against oxidative stress inducers (hydrogen peroxide and iron)
PB MDPI
YR 2019
FD 2019
LK http://hdl.handle.net/10347/23521
UL http://hdl.handle.net/10347/23521
LA eng
NO Chavarria, D.; Fernandes, C.; Aguiar, B.; Silva, T.; Garrido, J.; Remião, F.; Oliveira, P.J.; Uriarte, E.; Borges, F. Insights into the Discovery of Novel Neuroprotective Agents: A Comparative Study between Sulfanylcinnamic Acid Derivatives and Related Phenolic Analogues. Molecules 2019, 24, 4405
NO This project was supported by Foundation for Science and Technology (FCT) and FEDER/COMPETE research grants (UID/QUI/00081, NORTE-01–0145-FEDER-000028, POCI-01–0145-FEDER-029164). D. Chavarria, C. Fernandes and T. Silva grants are supported by FCT, POPH and FEDER/COMPETE and NORTE-01-0145-FEDER-000028.This article is based upon work from COST Action CA15135
DS Minerva
RD 24 abr 2026