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J Med Chem ; 61(4): 1609-1621, 2018 02 22.
Artículo en Inglés | MEDLINE | ID: mdl-29406740

RESUMEN

The plant metabolite 3,4,5-tri-O-galloylquinic acid methyl ester (TGAME, compound 6) was synthesized, and its potential effect on calcium oxalate monohydrate (COM) crystal binding to the surface of Madin-Darby canine kidney cells type I (MDCKI) and crystal growth in a Drosophila melanogaster Malpighian tubule (MT) model were investigated. Membrane, cytosolic, and total annexin A1 (AxA1), α-enolase, and heat shock protein 90 (HSP90) amounts were examined by Western blot analysis after subcellular fractionation, then confirmed by immunofluorescence staining of cultured cells. Pretreatment of MDCKI cells with TGAME for up to 6 h significantly diminished COM crystal binding in a concentration-dependent manner. TGAME significantly inhibited AxA1 surface expression by immunofluorescence microscopy, whereas intracellular AxA1 increased. Western blot analysis confirmed AxA1 expression changes in the membrane and cytosolic fractions of compound-treated cells, whereas whole cell AxA1 remained unchanged. TGAME also significantly decreased the size, number, and growth of calcium oxalate (CaOx) crystals induced in a Drosophila melanogaster MT model and possessed a potent antioxidant activity in a DPPH assay.


Asunto(s)
Anexina A1/efectos de los fármacos , Oxalato de Calcio/química , Adhesión Celular/efectos de los fármacos , Ácido Gálico/análogos & derivados , Ácido Quínico/análogos & derivados , Animales , Anexina A1/metabolismo , Antioxidantes , Línea Celular , Cristalización , Perros , Drosophila melanogaster , Ácido Gálico/síntesis química , Ácido Gálico/química , Ácido Gálico/farmacología , Células de Riñón Canino Madin Darby/efectos de los fármacos , Células de Riñón Canino Madin Darby/metabolismo , Túbulos de Malpighi/química , Ácido Quínico/síntesis química , Ácido Quínico/química , Ácido Quínico/farmacología , Fracciones Subcelulares/química , Fracciones Subcelulares/metabolismo
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