Abstract:
: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.
journal_name
J Med Chemjournal_title
Journal of medicinal chemistryauthors
Abd El-Salam M,Bastos JK,Han JJ,Previdi D,Coelho EB,Donate PM,Romero MF,Lieske Jdoi
10.1021/acs.jmedchem.7b01566subject
Has Abstractpub_date
2018-02-22 00:00:00pages
1609-1621issue
4eissn
0022-2623issn
1520-4804journal_volume
61pub_type
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