title: 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 alpha, beta-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.
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Ataturk University, Erzurum, Turkey.
authors.forename: Halise Inci
authors.initials: HI
authors.lastname: Gul
authors.forename: Murat
authors.initials: M
authors.lastname: Cizmecioglu
authors.forename: Sevil
authors.initials: S
authors.lastname: Zencir
authors.forename: Mustafa
authors.initials: M
authors.lastname: Gul
authors.forename: Pakize
authors.initials: P
authors.lastname: Canturk
authors.forename: Mustafa
authors.initials: M
authors.lastname: Atalay
authors.forename: Zeki
authors.initials: Z
authors.lastname: Topcu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002417:Cattle; D002460:Cell Line; D047188:Chalcones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D004264:DNA Topoisomerases, Type I / Q000378:metabolism; D006801:Humans; D020128:Inhibitory Concentration 50; D019169:Jurkat Cells; D010957:Plasmids / Q000378:metabolism; D059004:Topoisomerase I Inhibitors
chemical_list: D000970:Antineoplastic Agents; D047188:Chalcones; D059004:Topoisomerase I Inhibitors; C451019:4-hydroxychalcone; D004264:DNA Topoisomerases, Type I