A novel cyclic dinuclear gold(i) complex induces anticancer activity via an oxidative stress-mediated intrinsic apoptotic pathway in MDA-MB-231 cancer cells

Abstract

A new dinuclear cyclic gold(I) complex [Au2(DCyPA)2](PF6)2, 1 based on bis[2-(dicyclohexylphosphano)ethyl]amine (DCyPA) has been synthesized and characterized by elemental analysis, IR and NMR spectroscopies, and X-ray crystallography. In the dinuclear...

Novel dinuclear gold(i) complexes containing bis(diphenylphosphano)alkanes and (biphenyl-2-yl)(di-tert-butyl)phosphane: synthesis, structural characterization and anticancer activity

“…Furthermore, we have recently shown that the cyclic gold(I) complex of bis[2-(dicyclo-hexylphosphano)ethyl]amine showed an effective anticancer response against the triple-negative breast cancer cells (MDA-MB-231), which was mediated via oxidative stress-mediated activation of intrinsic apoptosis. 14 Here, we speculate that exposure to complexes 1-4 may proceed through similar mechanisms that are associated with the disruption of the DC m and potential activation of the intrinsic apoptotic pathway. It is worth mentioning that other mechanisms of toxicity cannot be ruled out.…”

“…In the IR spectra of the complexes (1-4), the n(P-C) bands of phosphane ligands were observed around 1100 cm À1 and 1000 cm À1 . 14,15 The n(CQC) modes of the aromatic ring were detected at about 1470 cm À1 . The medium intensity bands in the region of 2900 cm À1 in the IR spectra are assigned to n(C-H)(aliphatic) vibrations, while those above 3000 cm À1 represent the aromatic C-H stretches.…”

“…The coordination geometry around the gold(I) atom is distorted linear with a (P-Au-P) bond angle of 170.79(4) o , 175.29(4) o and 175.18(4) o for 1, 2 and 4 respectively, which is typical for such type of gold(I)-phosphane complexes. 2,7,14,[33][34][35] The phosphorus atoms of both phosphanes in the complexes possess a tetrahedral environment. The Au-P bond lengths, which vary from 2.29(11) to 2.33(12) Å for the complexes, are similar to those reported for the analogous compounds; 2,7,14,33-37 for example, 2.3013(13)-2.3129(13 36 However, these distances are relatively shorter than in the tetrahedrally coordinated complex, [Au(Dppp)(PPh 3 )Cl] (2.39(13) Å).…”

“…Anticancer gold(I) complexes bearing phosphane ligands have been an attractive field of research over the past few years. [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16] The antirheumatic drug auranofin [(2,3,4,6-tetra-O-acetyl-L-thiob-D-glyco-pyranosato-S-)(triethylphosphane)gold(I)] 17,18 has demonstrated remarkable cytotoxic activity in various in vitro and in vivo tumor models including the cisplatin-resistant cell lines. [19][20][21][22][23][24][25] Importantly, the Messori group has demonstrated that the presence of the thiosugar moiety in auranofin is not essential for its pharmacological action, suggesting that the tuning of some relevant chemical properties, such as lipophilicity, could be exploited to improve its bioavailability without losing its antiproliferative properties.…”

“…40 Mitochondria were regarded as the primary targets in apoptosis induced by the mixed phosphine gold species in melanoma cell lines. 41 Considering these studies and in continuation of our focus on the structural and antitumor properties of the gold(I) complexes of phosphanes, [13][14][15][16][42][43][44][45] we report here the synthesis of a novel series of gold(I) complexes (1-4) containing both mono-phosphane {(biphenyl-2-yl)di-tert-butylphosphane, Bdbp} and diphosphanes {1,2-bis(diphenylphosphano)ethane, Dppe; 1,3-bis(diphenylphosphano)propane, Dppp; 1,4-bis(diphenylphosphano)butane, Dppb and bis [2-(diphenylphosphano)methyl]amine, Dpma} ligands. The complexes were characterized by FTIR, NMR ( 1 H and 13 C) spectroscopic methods, and their structures were determined by single crystal X-ray diffraction analysis.…”