Evaluation of biological activity of selected tert-butylquinone derivatives as potential antitumor drugs

Abstract

The biological activity of selected of 2-tert-butyl-1.4-benzoquinone (TBQ) and its derivatives: 2-tert-buty|-5-(isopropylthio)-1.4-benzoquinone, 2-tert-butyl-5-(propylthio)-1.4-benzoquinone, 2-tert-butyl-5,6-(ethylendithio)-1.4-benzoquinone, 2-tert-butyl-5-(phenylthio)-1.4-benzoquinone and 2-tert-butyl-6-(phenyithio)-1.4-benzoquinone was examined by their antibacterial, toxic, cytotoxic and genotoxic potential. The antimicrobial potential of derivatives was investigated by the broth microdilution method establishing minimal inhibitory concentration for 4 gram-negative and 4 gram-positive bacteria. Toxicity has been tested by 24 h treatment of Artemia nauplii by ARC test. Cytotoxicity was assessed in 24 h treatment in three different cell lines with MTT and MTS assay: human fetal lung cell line (MRC-5), human cancer cell line - melanoma (HS 294T) and human liver cancer cell line (HepG2). Genotoxicity was evaluated after 24 h treatment by comet assay in MRC-5 and HepG2 cell lines. In general, result indicated that modification of TBQ enhanced its activity. All substances exhibited antibacterial potential but only against gram-positive bacteria whereas 2-tert-butyl-5,6-(ethylendithio)-1.4-benzoquinone showed the strongest antibacterial activity. Results of ARC test indicated that synthesized derivatives (with exception of 2-tert-butyl-6-(phenylthio)-1.4-benzoquinone) lose their toxic potential in comparison with parent compound TBQ. Derivatives exhibited stronger cytotoxic activity a all three cell lines in comparison with TBQ, agan 2-tert-butyl-5,6-(ethylendithio)-1.4-benzoquinone. Results of the comet assay derivatives showed the strongest activity also have indicated stronger genotoxic, potential in comparison with TBQ itself indicating that DNA damage could be one of the pathmay in cytotoxicity induction.