Several new organogold(III) derivatives of the type [AuX(2)(damp)] (damp = o-C(6)H(4)CH(2)NMe(2)) have been prepared [X = CN, SCN, dtc, or X(2) = tm; dtc = R(2)NCS(2) (R = Me (dmtc) or Et (detc)); tm = SCH(CO(2))CH(2)CO(2)Na] together with [AuCl(tpca)(damp)]Cl (tpca = o-Ph(2)PC(6)H(4)CO(2)H), [Au(dtc)(damp)]Y (Y = Cl, BPh(4)) and K[Au(CN)(3)(damp)]. The (13)C NMR spectra of these and previous derivatives have been fully assigned. In [Au(dtc)(2)(damp)] and K[Au(CN)(3)(damp)], the damp ligand is coordinated only through carbon, as shown by X-ray crystallography and/or NMR. [Au(detc)(2)(damp)] has space group C2/c, with a = 29.884(4) Å, b = 13.446(2) Å, c = 12.401(2) Å, beta = 99.45(3)(o), V = 4915 Å(3), Z = 8, and R = 0.057 for 1918 reflections. The damp and one detc ligand are monodentate, the other detc is bidentate; in solution, the complex shows dynamic behavior, with the detc ligands appearing equivalent. The crystal structure of [Au(dmtc)(damp)]BPh(4) [Pna2(1), a = 26.149(5) Å, b = 11.250(2) Å, c = 11.921(2) Å, V = 3507 Å(3), Z = 4, R = 0.073, 1772 reflections] shows both ligands to be bidentate in the cation, but the two Au-S distances are nonequivalent. The crystal structure of [Au(tm)(damp)] has also been determined [P2(1)/n, a = 18.267(7) Å, b = 9.618(3) Å, c = 18.938(4) Å, beta = 113.45(3)(o), V = 3053 Å(3), Z = 8, R = 0.079, 1389 reflections]. The tm is bound through sulfur and the carboxyl group which allows five-membered ring formation. In all three structures, the trans-influence of the sigma-bonded aryl group is apparent. [AuCl(2)(damp)] has been tested in vitroagainst a range of microbial strains and several human tumor lines, where it displays differential cytotoxicity similar to that of cisplatin. Against the ZR-75-1 human tumor xenograft, both [AuCl(2)(damp)] and cisplatin showed limited activity.
Four analogues of the gold(III) complex [AuCl2(damp)] (1) (damp = 2-[(dimethylamino)methyl]phenyl) have been evaluated for antitumor activity. The compounds have structural features in common with cisplatin which was included as a comparison in the study. In vitro, against a panel of cell lines established from tumors of different tissue types, the gold complexes showed broadly similar growth inhibitory properties with some selectivity to the HT1376 bladder cell line. In a panel of human ovarian carcinoma cell lines, non-cross-resistance to cisplatin was observed, for the complexes, in an acquired cisplatin-resistant line. In vivo, using subcutaneously implanted xenografts derived from the HT1376 bladder and CH1 ovarian cell lines, [Au(acetato)2(damp)] (3) and [Au(malonato)(damp)] (5) (administered intraperitoneally) gave significant tumor inhibition. Mechanistic studies performed with compound 3 showed marked differences to cisplatin. Thus, much higher concentrations of the gold compound were required to affect Col E1 plasmid mobility, and an alkaline elution study showed that 3 did not cause interstrand DNA cross-links in SK-OV-3 cells. Exposure of SK-OV-3 cells to 3 induced only relatively minor changes in cell cycle distribution. Furthermore 3 was only marginally active in vivo against the cisplatin-sensitive murine ADJ/PC6 plasmacytoma. In summary, the gold-(III) complexes 3 and 5 exhibited selective cytotoxicity in vitro and showed in vivo antitumor activity against human carcinoma xenografts. Also, although 3 has some structural similarity to cisplatin, its mode of action appears to be different.
Recebido em 23/4/97; aceito em 17/12/97 SYNTHESIS AND CHARACTERIZATION OF NEW GOLD (I) PHOSPHINE COMPLEXES. In this contribution a few new gold(I)phosphine complexes, [2-(PPh 2)C 6 H 4 CO 2 H]AuX (where X = Cl, SCN, Br 3) and a similar gold(III) derivative [{2-(PPh 2)C 6 H 4 CO 2 H}Au III Cl (C 6 H 4 CH 2 NMe 2)]Cl have been synthesised and characterised. The phosphine, 2-(diphenylphosphino)benzoic acid, has been employed for the first time in gold chemistry. This ligand is potentially bidentate through bonding of the phosphine and carboxylate groups. The X-ray structure of the complex chloro[2-(diphenylphosphino) benzoic acid]gold(I) has been elucidated and the bond lengths encountered show great similarity to those of chloro(triphenylphosphine)gold(I). [2-(PPh 2)C 6 H 4 CO 2 H]AuCl crystallises in the space group P2 1 /c with a = 9.113(2) Å, b = 10.925(2) Å, c = 23.069(4) Å, β = 99.95 o (3), V = 2299 Å 3 , Z = 4 and R = 0.091. Biological tests for anti-fungal and anti-bacterial activity demostrate that [2-(PPh 2)C 6 H 4 CO 2 H]AuCl exhibits broad spectrum activity against a range of organisms.
It is evident that the chemistry of platinum is in a more advanced state than that of gold, mainly due to the success of the former in several anti-cancer drugs. With a view to finding possible, new candidates with chemotherapeutic potential, the use of sulphur-donor ligands bonded to platinum and gold is discussed herein in an attempt to promote the need to investigate similar ligands. Chloro(2,3-diphenyl-l,3,4-thiadiazolium-5-thiolato-Sexo)gold(I) has been synthesised using a standard reaction, whereby Au(lll) is initially reduced to Au(I) then reacted with the ligand, 2,3-diphenyl-l,3,4-thiadiazolium-5-thiolate.hydrochloride, isolated and finally characterised by elemental analyses and infrared spectroscopy. The compound is the first example of gold attached to a meso-ionic compound. It has also been tested for anti-bacterial and anti-fungal activity and shown to possess moderate activity against Gram-positive bacteria, although is inactive against Gram-negative bacteria and fungi.
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