Heterocyclic β-keto sulfide derivatives of carvacrol: Synthesis and copper (II) ion reducing capacity

Alexander H Cocolas; Eden L Parks; Andrew J Ressler; Mia H Havasi; Navindra P Seeram; Geneive E Henry

doi:10.1016/j.bmcl.2019.126636

Heterocyclic β-keto sulfide derivatives of carvacrol: Synthesis and copper (II) ion reducing capacity

Bioorg Med Chem Lett. 2019 Oct 1;29(19):126636. doi: 10.1016/j.bmcl.2019.126636. Epub 2019 Aug 24.

Authors

Alexander H Cocolas¹, Eden L Parks¹, Andrew J Ressler¹, Mia H Havasi¹, Navindra P Seeram², Geneive E Henry³

Affiliations

¹ Department of Chemistry, Susquehanna University, 514 University Avenue, Selinsgrove, PA 17870, USA.
² Bioactive Botanical Research Laboratory, Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, Kingston, RI 02881, USA.
³ Department of Chemistry, Susquehanna University, 514 University Avenue, Selinsgrove, PA 17870, USA. Electronic address: henry@susqu.edu.

PMID: 31474483
DOI: 10.1016/j.bmcl.2019.126636

Abstract

Sixteen β-keto sulfide derivatives of carvacrol (4-19) incorporating phenyl or N, O and S heterocyclic moieties were synthesized in three steps. The relationships between heterocyclic structure and cupric, Cu(II), ion reducing antioxidant capacity (CUPRAC) were examined. Nine of the compounds (8-9 and 13-19) showed better CUPRAC activity than trolox at neutral pH, with trolox equivalent antioxidant capacity (TEAC) coefficients ranging between 1.20 and 1.75. Two derivatives (11-12) showed comparable reducing capacity to trolox, with TEAC values of 0.95 for 11 and 1.02 for 12. Compounds 8-9 and 11-19 were more effective at reducing the Cu(II) ion than ascorbic acid and the parent compound, carvacrol. The most effective antioxidants were those containing an oxadiazole, thiadiazole or triazole moiety. In particular, the methyl thiadiazole derivative (15) had the highest Cu(II) ion reducing capacity, with a TEAC coefficient of 1.73.

Keywords: Antioxidant; Carvacrol; Copper (II) ion reduction; Heterocyclic β-keto sulfides.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Antioxidants / chemical synthesis*
Antioxidants / pharmacology*
Chromans / pharmacology
Copper / chemistry*
Cymenes / chemistry*
Heterocyclic Compounds / chemistry*
Molecular Structure
Sulfides / chemistry*

Substances

Antioxidants
Chromans
Cymenes
Heterocyclic Compounds
Sulfides
Copper
carvacrol
6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid

Grants and funding

P20 GM103430/GM/NIGMS NIH HHS/United States