Modification of intracellular free calcium in cultured F2408 embryo fibroblasts by 3-substituted-2-thiohydantoin derivatives.
3-substituted-2-thiohydantoin derivatives were synthesized and their structures elucidated by IR, 1H-NMR spectroscopy and elemental analysis. The cytotoxicity of the 2-thiohydantoin derivatives to rat embryo fibroblasts (F2408) in vitro was determined, and the effects of these compounds on intracellular free Ca2+, [Ca2+]i, were measured by spectrofluorophotometry. Cytotoxicity was determined by metabolic reduction of a tetrazolium salt to a formazan dye (MTT assay). Compounds 4 and 7 showed cytotoxic activity, with IC50 values in the range of 1-1.2 microM. Introduction of either chlorophenyl, metoxyphenyl, nitrophenyl or benzyl groups at C-3 resulted in concentration-dependent cytotoxic effects. Compounds 1-6 at 1 microM or more significantly increased [Ca2+]i in a dose-dependent manner in the cultured fibroblasts. This action may have been mediated through intracellular calcium stores.
Incesu
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Department of Biochemistry, Faculty of Pharmacy, Anadolu University, Eskisehir, Turkey. zseller@anadolu.edu.tr
Benkli
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Akalin
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Kaplancikli
Z A
ZA
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects*; D002478:Cells, Cultured; D004622:Embryo, Mammalian; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D013867:Thiohydantoins / Q000032:analysis / Q000494:pharmacology*
D013867:Thiohydantoins; D002118:Calcium