Antioxidant properties of thio-caffeine derivatives: Identification of the newly synthesized 8-[(pyrrolidin-1-ylcarbonothioyl)sulfanyl]caffeine as antioxidant and highly potent cytoprotective agent. Issue 16 (15th August 2016)

• Record Type: Journal Article
• Authors: Jasiewicz, Beata; Sierakowska, Arleta; Wandyszewska, Natalia; Warżajtis, Beata; Rychlewska, Urszula; Wawrzyniak, Rafał; Mrówczyńska, Lucyna
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 26:Issue 16(2016)
• Page Start: 3994
• Page End: 3998
• Publication Date: 2016-08-15
• Subjects: Caffeine thioderivatives -- Antioxidant activity -- Haemolysis -- Human erythrocytes -- Trolox -- X-ray structure; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2016.06.091
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: C8-substitution of caffeine molecule by (pyrrolidin-1-yl)carbothioylsulfanyl group results in tremendous increase of antioxidant and cytoprotective in vitro activity of this novel, highly functionalized compound. 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 0.1 mg/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.