Synthesis and biological activity of alkylthio and arylthio derivatives of tert-butylquinone

• Published in: Journal of the Serbian Chemical Society Vol. 87; no. 11; pp. 1245 - 1258
• Main Authors: Djordjevic, Jelena, Kolarevic, Stoimir, Jovanovic-Maric, Jovana, Oaldje-Pavlovic, Mariana, Sladic, Dusan, Novakovic, Irena, Vukovic-Gacic, Branka
• Format: Journal Article
• Language: English
• Published: Serbian Chemical Society 2022
• Subjects: antibacterial activity; antioxidant activity; comet test; mtt assay; tbq; toxicity
• ISSN: 0352-5139; 1820-7421
• DOI: 10.2298/JSC220304044D

Biological activity of 2-tert-butyl-1,4-benzoquinone (TBQ) and its derivatives, 2-tert-butyl-5-(2-propylthio)-1,4-benzoquinone, 2-tert-butyl-5- -(propylthio)-1,4-benzoquinone, 2-tert-butyl-5,6-(ethylenedithio)-1,4-benzoquinone, 2-tert-butyl-5-(phenylthio)-1,4-benzoquinone and 2-tert-butyl-6-(phenylthio)- 1,4-benzoquinone, were tested for their antioxidant, antibacterial, toxic, cytotoxic and genotoxic potential. Using the DPPH test, all derivatives showed good antioxidant activity, better than ascorbic acid, and the 2-tert- -butyl-5-(propylthio)-1,4-benzoquinone derivative showed the strongest effect. Better antibacterial potential was observed against Gram-positive bacteria in the broth microdilution method in which the 2-tert-butyl-5-(phenylthio)-1,4- -benzoquinone derivative showed the strongest activity (MIC = 15.6 ?M). The results of toxicity tests, using the Brine shrimp test, indicated that the derivatives lose their toxic potential compared to TBQ, except for 2-tert-butyl-6- -(phenylthio)-1,4-benzoquinone, which showed a 3 times stronger effect. Cytotoxicity was assessed by the MTT assay in 24 and 72 h treatments in MRC-5, HS 294T and A549 cell lines in threefold decreasing gradient (11, 33 and 100 ?M). Modifications potentiate the cytotoxic effect, and the strongest effect was observed with the 2-tert-butyl-5,6-(ethylendithio)-1,4-benzoquinone derivative. In addition, the genotoxic potential was examined in the MRC-5 cell line using the comet assay. All tested derivatives of TBQ showed a genotoxic effect at all applied subtoxic concentrations. In general, the chemical modifications of TBQ enhanced its biological activity.