title: Comparison of effects of some cyclic chalcone analogues on selected mitochondrial functions.
abstract: In earlier studies, cytotoxity of chalcones (1) and cyclic chalcone analogues E-2-arylidene-tetralones (2) and -benzosuberones (3) towards various murine and human tumour cells has been tested. Preliminary biochemical investigations showed the compounds to inhibit protein and DNA syntheses. It was also found that the compounds affect the cellular thiol status of the treated cells. In order to gain new insights into the cytotoxic mechanism of the compounds effects of some previously investigated 2 and 3 derivatives on isolated rat liver mitochondria was investigated. It was found that the most cytotoxic compounds 2c and 3b significantly decreased the GSH level of the mitochondria. Incubation of the investigated chalcones with reduced GSH under cell-free conditions indicated spontaneous conjugation (non-redox) reaction at pH 7.4 and pH 9.0. Investigation of antioxidant capacity of the compounds by monitoring time course of the Fenton-reaction initiated in vitro degradation of 2-deoxyribose showed the compounds to display hydroxyl radical scavenger activity. Investigation of respiratory control ratio of 2c and 3b showed the compounds to display an inhibitory effect on respiration, compound 2b, however, displayed rather an uncoupling effect. The experiments provide further details of cytotoxic effects of the synthetic chalcones displaying dual - cytotoxic and cytoprotective - effects.
authors.affiliation: Institute of Pharmaceutical Chemistry, Faculty of Medicine, University of Pécs, Pécs, Hungary.
authors.forename: P
authors.initials: P
authors.lastname: Perjési
authors.forename: J
authors.initials: J
authors.lastname: Kubálková
authors.forename: Z
authors.initials: Z
authors.lastname: Chovanová
authors.forename: M
authors.initials: M
authors.lastname: Mareková
authors.forename: Z
authors.initials: Z
authors.lastname: Rozmer
authors.forename: K
authors.initials: K
authors.lastname: Fodor
authors.forename: Z
authors.initials: Z
authors.lastname: Chavková
authors.forename: V
authors.initials: V
authors.lastname: Tomecková
authors.forename: J
authors.initials: J
authors.lastname: Guzy
mesh_terms: D000251:Adenosine Triphosphatases / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D047188:Chalcones / Q000494:pharmacology*; D002855:Chromatography, Thin Layer; D003855:Deoxyribose; D005978:Glutathione / Q000378:metabolism; D017665:Hydroxyl Radical / Q000737:chemistry; D066298:In Vitro Techniques; D007202:Indicators and Reagents; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008930:Mitochondria, Liver / Q000187:drug effects*; D010084:Oxidation-Reduction; D010101:Oxygen Consumption / Q000187:drug effects; D051381:Rats; D013055:Spectrophotometry, Infrared; D013438:Sulfhydryl Compounds / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000975:Antioxidants; D047188:Chalcones; D007202:Indicators and Reagents; D013438:Sulfhydryl Compounds; D017665:Hydroxyl Radical; D003855:Deoxyribose; D000251:Adenosine Triphosphatases; D005978:Glutathione