Cytotoxic activity of 4′-hydroxychalcone derivatives against Jurkat cells and their effects on mammalian DNA topoisomerase I

Abstract

Chalcones (1,3-diaryl-2-propen-1-ones) are α, β-unsaturated ketones with cytotoxic and anticancer properties. Several reports have shown that compounds with cytotoxic properties may also interfere with DNA topoisomerase functions. Five derivatives of 4′-hydroxychalcones were examined for cytotoxicity against transformed human T (Jurkat) cells as well as plasmid supercoil relaxation experiments using mammalian DNA topoisomerase I. The compounds were 3-phenyl-1-(4′-hydroxyphenyl)-2-propen-1-one (I), 3-(p-methylphenyl)-1-(4′-hydroxyphenyl)-2-propen-1-one (II), 3-(p-methoxyphenyl)-1-(4′-hydroxyphenyl)-2-propen-1-one (III), 3-(p-chlorophenyl)-1-(4′-hydroxyphenyl)-2-propen-1-one (IV), and 3-(2- thienyl)-1-(4′-hydroxyphenyl)-2-propen-1-one (V). The order of the cytotoxicity of the compounds was; IV > III > II > I > V. Compound IV, had the highest Hammett and log P values (0.23 and 4.21, respectively) and exerted both highest cytotoxicity and strongest DNA topoisomerase I inhibition. Compounds I and II gave moderate interference with the DNA topoisomerase I while III & V did not interfere with the enzyme.

Keywords::

• 4′-hydroxychalcone
• cytotoxicity
• Jurkat cells
• MTT
• DNA topoisomerase I
• inhibition

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

Notes

^* Present Address: Department of Biochemistry, Faculty of Science, Ege University, Izmir, Turkey