Inhibition of the cathepsin cysteine proteases B and K by square-planar cycloaurated gold(III) compounds and investigation of their anti-cancer activity

Structural and spectroscopic studies of Au(III) and Pd(II) chloride complexes and organometallics with 2-benzylpyridine

“…Its d H6 and d CH2 parameters in CD 2 Cl 2 and DMSO-d 6 are in agreement to the literature values [1,4]. A similar behaviour was reported for analogous [Au(LL Ã )Cl 2 ] organometallics with many other 2-arylpyridines (LL = 2ppy [19,22,47,48], 2-benzoylpyridine [7,49], 2-phenoxypyridine and 2-phenylsulfanylpyridine [46], 2-phenylaminopyridine and 2-phenyl(N-methyl)aminopyridine [46,50]). …”

“…The H(3 0 ) atom, adjacent to the metallated C(2 0 ) carbon, is moderately deshielded while the other protons are weakly shielded (D [7]. A similar inequivalency was noted for the two C(CH 3 ) 2 methyl groups in [Au (2-(1,1-dimethylbenzyl)pyridine à )Cl 2 ] (d CH3 : 2.35 ppm vs 2.06 ppm), being also proved by single crystal X-ray studies (ZETYAY [1]).…”

“…These compounds are of increasing interest due to their catalytic properties (trans-[Pd(2bzpy) 2 Cl 2 ] in hydrogenation of unsaturated functional groups [5], [Au(2bzpy à )Cl 2 ] in introduction of amine and alkyne substituents into oligosaccharides [6]) and cytotoxicity ([Au(2bzpy à )Cl 2 ] is active against cancer [7] and parasites [8]). [Au(2bzpy à )Cl 2 ] and its [Au(2-(1,1-dimethylbenzyl)pyridine à )Cl 2 ] analogue are also widely used as precursors for preparation of some other compounds with antitumour, antibacterial, antifungal or antiviral properties [9][10][11][12][13][14][15][16][17].…”

“…In DMSO-d 6 , their average deshielding is similar to that for [Au(2ppy à )Cl 2 ] (mean D Hð3ÞÀHð6Þ coord : 0.63 ppm vs 0.55 ppm [22]), and the same concerns H(6) (D Hð6Þ coord : 0.69 ppm vs 0.86-0.87 ppm [19,22,47,48]). In CDCl 3 , H(6) is much more deshielded that in [Au(2bzpy)Cl 3 ] (D Hð6Þ coord : 0.79 ppm vs 0.14 ppm), such D Hð3Þ coord;½AuðLL à ÞCl2 ) D Hð6Þ coord;½AuðLLÞCl3 relation being also noted for [Au(2ppy à )Cl 2 ] vs [Au(2ppy)Cl 3 ] (0.86-0.87 ppm ) 0.15 ppm [19,21,22,47,48]), and for (R)/(S)-[Au(2-(1-methylbenzyl)pyridine à )Cl 2 ] vs [Au(2-(1-methylbenzyl)pyridine)Cl 3 ] (0.72/ 0.82 ppm ) 0.08 ppm [1]);Table S3.Similarly high D Hð6Þ coord values were reported for some other [Au(LL à )Cl 2 ] organometallics with derivatives of 2ppy (LL = 2-(4-methylphenyl)pyridine, 4-(n-propyl)-2-phenylpyridine, 2-(2,4-difluorophenyl)pyridine: D Hð6Þ coord = 0.86-1.13 ppm[4,48,51]) or 2bzpy (LL = 3-methyl-2-benzylpyridine, 4-methyl-2-benzylpyridine, 5-methyl-2-benzylpyridine, 2-(6-methylbenzyl)pyridine, 2-(5-methylbenzyl) pyridine, 2-(4-methylbenzyl)pyridine, 2-(4-phenylbenzyl)pyridine, 2-(4-chlorobenzyl)pyridine, 2-(1,1-dimethylbenzyl)pyridine, 2-(1-phenylbenzyl)pyridine: D Hð6Þ coord = 0.45-0.82 ppm[1,7]);…”

Exploring the potential of gold(iii) cyclometallated compounds as cytotoxic agents: variations on the C^N theme

“…8 For example, Fricker and coworkers reported the synthesis and biological activity of square-planar six-membered cycloaurated Au(III) compounds with a pyridinyl-phenyl linked backbone and two monodentate or one bidentate leaving group(s), which were able to inhibit the cysteine proteases cathepsins B and K in vitro. 22 Structure/activity relationships were investigated by modifications to the pyridinyl-phenyl backbone, and leaving groups, demonstrating optimal activity with substitution at the 6 position of the pyridine ring. In this study, the importance of the leaving groups was also highlighted.…”