title: Antioxidant properties of thio-caffeine derivatives: Identification of the newly synthesized 8-[(pyrrolidin-1-ylcarbonothioyl)sulfanyl]caffeine as antioxidant and highly potent cytoprotective agent.
abstract: A series of nine thio-caffeine analogues were synthesized and characterised by NMR, FT-IR and MS spectroscopic methods. Molecular structures of four of them were determined using single crystal X-ray diffraction methods. The antioxidant properties of all compounds, at concentration ranges from 0.025 to 0.1mg/mL, were evaluated by various chemical- and cell-based antioxidant assays. Human erythrocytes were used to examine in vitro haemolytic activity of all compounds and their protective effect against oxidative haemolysis induced by AAPH, one of the commonly used free radical generator. All compounds studied showed no effect on the human erythrocytes membrane structure and permeability with the exception of 8-(phenylsulfanyl)caffeine. Among the nine caffeine thio-analogues tested, the newly synthesized 8-[(pyrrolidin-1-ylcarbonothioyl)sulfanyl]caffeine possessed exceptionally high antioxidant properties. Moreover, it protects human erythrocytes against AAPH-induced oxidative damage as efficiently as the standard antioxidant Trolox. Therefore, 8-[(pyrrolidin-1-ylcarbonothioyl)sulfanyl]caffeine may have a significant cytoprotective potential caused by its antioxidant activity.
authors.affiliation: Faculty of Chemistry, Adam Mickiewicz University, Umultowska 89b, 61-614 Poznań, Poland. Electronic address: beatakoz@amu.edu.pl.
authors.forename: Beata
authors.initials: B
authors.lastname: Jasiewicz
authors.affiliation: Faculty of Chemistry, Adam Mickiewicz University, Umultowska 89b, 61-614 Poznań, Poland.
authors.forename: Arleta
authors.initials: A
authors.lastname: Sierakowska
authors.affiliation: Department of Cell Biology, Faculty of Biology, Adam Mickiewicz University, Umultowska 89, 61-614 Poznań, Poland.
authors.forename: Natalia
authors.initials: N
authors.lastname: Wandyszewska
authors.affiliation: Faculty of Chemistry, Adam Mickiewicz University, Umultowska 89b, 61-614 Poznań, Poland.
authors.forename: Beata
authors.initials: B
authors.lastname: Warżajtis
authors.affiliation: Faculty of Chemistry, Adam Mickiewicz University, Umultowska 89b, 61-614 Poznań, Poland.
authors.forename: Urszula
authors.initials: U
authors.lastname: Rychlewska
authors.affiliation: Faculty of Chemistry, Adam Mickiewicz University, Umultowska 89b, 61-614 Poznań, Poland.
authors.forename: Rafał
authors.initials: R
authors.lastname: Wawrzyniak
authors.affiliation: Department of Cell Biology, Faculty of Biology, Adam Mickiewicz University, Umultowska 89, 61-614 Poznań, Poland. Electronic address: lumro@amu.edu.pl.
authors.forename: Lucyna
authors.initials: L
authors.lastname: Mrówczyńska
mesh_terms: D000975:Antioxidants / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D002110:Caffeine / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D018360:Crystallography, X-Ray; D004912:Erythrocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D008968:Molecular Conformation; D020011:Protective Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D017550:Spectroscopy, Fourier Transform Infrared; D013438:Sulfhydryl Compounds / Q000737:chemistry*
chemical_list: D000975:Antioxidants; D020011:Protective Agents; D013438:Sulfhydryl Compounds; D002110:Caffeine
keywords: Antioxidant activity; Caffeine thioderivatives; Haemolysis; Human erythrocytes; Trolox; X-ray structure