Effect of selected dimethylaminochalcones on some mitochondrial activities

Abstract

Chalcones and their synthetic cyclic analogues have been shown to possess a full scale of biological activities in a variety of experimental systems. They were assessed to be mostly effective in defense against free radicals in the organism, but several compounds exhibited cytotoxic pro-oxidant activities. The respiratory response and antioxidant status in mitochondria were investigated upon addition of 4'-dimethylaminochalcone (1a) and its cyclic analogues, (E)-2-(4'-((CH3)2 N)-benzylidene)-1-indanone (1b), -1-tetralone (1c), and -1-benzosuberone (1d). Selected structures were able to change the respiratory response of mitochondria and showed an ability to modify mitochondrial metabolic and redox efficiency, though they did not indicate redox reactivity towards glutathione in adduct-free incubations. The results of the study indicate that -chalcone and -tetralone derivatives cause suppression of reactive oxygen species affecting mitochondrial respiration by mild uncoupling. In addition, (E)-2-(4'-((CH3)2 N)-indanone (1b), and to a greater extent, -benzosuberone (1d), showed pro-oxidant effects, which partially explain their cytotoxicity.

Synthesis and bioactivity studies on new 4-(3-(4-Substitutedphenyl)-3a,4-dihydro-3H-indeno[1,2-c]pyrazol-2-yl) benzenesulfonamides

“…The mixture was neutralized with hydrochloric acid (10% w/v, 10 mL). The colored precipitate formed was filtered and crystallized from waterethanol for the compounds (1-6) [13][14][15]17,40,41 . Chemical structure of the compounds 1-6 were confirmed by 1 H NMR, 13 C NMR, HRMS and the literature reported melting points of the compounds.…”

“…Indane or indanone-bearing compounds had been reported to show their several bioactivities including cytotoxic/anticancer activities [8][9][10][11][12][13][14][15] , inhibition of b-amyloid plaques, which were stimulated by acetylcholinesterase 16 , and effects on mitochondrial respiration by inhibition of reactive oxygen species 17 .…”

Introductory Chapter: Unregulated Mitochondrial Production of Reactive Oxygen Species in Testing the Biological Activity of Compounds

“…arylmethylene-1-indanone, (E)-2-arylmethylene-1-tetralone, and (E)-2-arylmethylene-benzosuberone) with several types of substituents, our studies were then primarily focused on monitoring their effects on mitochondria with respect to the production of ROS and the subsequent effects on selected antioxidant markers and ATP production. As the primary organ of xenobiotic metabolism in the body is the liver, studies with 4′-methyl-, methoxy- [16], 4′-hydroxy- [22], and 4′-dimethylamino-cyclic analogues of chalcones [23] were provided on mitochondria isolated from the rat liver. Analogues with methyl substituents showed rather a protective, antioxidant effect.…”