Study of dinuclear Rh(II) complexes of phenylalanine derivatives as potential anticancer agents by using X-ray fluorescence and X-ray absorption

Abstract

In vitro antitumor efficacy of several dinuclear bridgings and one chelate structure dirhodium(II) complex of N-protected phenylalanine derivatives were tested on HT-29 cells. The following synthesized and previously characterized complexes were applied in the present work: Rh-2(OAc)(4)(O-Phe-Z)(n) (n = 1-4, O--Phe-Z = N-benzyloxycarbonyl-L-phenylalaninate), Rh-2(OAc)(4-n)(O-Phe-Ac)(n) (n = 1-4, O--Phe-Ac = N-acetyl-L-phenylalaninate), Rh-2(OAc)(2)(N-Me-D-Phe-O)(2) corresponding to N-methyl-D-phenylalaninate as well as Rh-2(OAc)(4) (-OAc = acetate). Depending on the complex ligand type and its coordination number, the intracellular rhodium (Rh) content determined by total reflection X-ray fluorescence (TXRF) spectrometry in the HT-29 cells varied between 25 and 2500 ng/10(6) cells. In vitro cytotoxicity and cytostatic evaluations of the compounds on HT-29 human cell culture were performed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium assay. Compared to Rh-2(OAc)(4), the Rh compounds containing one or two O--Phe-Z moieties proved to be the most effective on the HT-29 cells. Moreover, synchrotron radiation TXRF-X-ray absorption near edge structure measurements suggested a change of the molecular symmetry of the dirhodium(II) center for the moderately in vitro cytotoxic, lipophilic L-phenylalanine derivative complexes, characterized also by low ligand exchange rate when they were studied on HT-29 cells. (C) 2015 Elsevier B.V. All rights reserved.