Anti-Tumor Activity, In Vitro and In Vivo, of Some Triphenylphosphinegold(I) Thionucleobases

The [Ph3PAu(6-MP)] complex, where 6-MPH is 6-mercaptopurine, is active against the cisplatinresistant cell line, mouse leukaemia L1210/DDP, as is the precursor compound [Ph3PAuCl], suggesting that the thiolate is not critical for activity. Against the human cell lines, FaDu (squamous cell carcinoma) and SKOV-3 (ovarian carcinoma), both [Ph3PAu(6-MP)] and [Ph3PAu(6-TG)], where 6-TGH is 6-thioguanine, were active. [Ph3PAu(6-MP)] was active against a murine PC6 plasmacytoma, but not as active as cisplatin

Preparation and Anti-Tumour Activity of Some Arylbismuth(III) Oxine Complexes

New arylbismuth(lll) oxinates, PhBi(MeOx)2, (p-MeC6H4)Bi(Ox)2, (p-MeC6H4)Bi(MeOx)2, (p-ClC6H4)Bi(Ox)2, and (p-ClC6H4)Bi(MeOx)2 (Ox− = quinolin-8-olate and MeOx−=2-methylquinolin-8-olate) have been prepared by reaction of the appropriate diarylbismuth chlorides with Na(Ox) or Na(MeOx) in the presence of 15-crown-5. An X-ray crystallographic study has shown PhBi(MeOx)2 to be a five coordinate monomer with distorted square pyramidal stereochemistry. Chelating MeOx ligands have a cisoid arrangement in the square plane and the phenyl group is apical. The lattice is stabilised by significant π-π interactions between centrosymmetric molecules. A range of these complexes has been shown to have high in vitro biological activity (comparable with or better than cisplatin) against L1210 leukaemia, the corresponding cisplatin resistant line, and a human ovarian cell line, SKOV-3. However, initial in vivo testing against a solid mouse plasmacytoma (PC6) and P388 leukaemia has not revealed significant activity

Preparation and anti-tumour activity of some arylbismuth(III) oxine complexes

New arylbismuth(lll) oxinates, PhBi(MeOx)₂, (p-MeC₆H₄)Bi(Ox)₂, (p-MeC₆H₄)Bi(MeOx)₂, (p-ClC₆H4)Bi(Ox)₂, and (p-ClC₆H₄)Bi(MeOx)₂ (Ox− = quinolin-8-olate and MeOx−=2-methylquinolin-8-olate) have been prepared by reaction of the appropriate diarylbismuth chlorides with Na(Ox) or Na(MeOx) in the presence of 15-crown-5. An X-ray crystallographic study has shown PhBi(MeOx)₂ to be a five coordinate monomer with distorted square pyramidal stereochemistry. Chelating MeOx ligands have a cisoid arrangement in the square plane and the phenyl group is apical. The lattice is stabilised by significant π-π interactions between centrosymmetric molecules. A range of these complexes has been shown to have high in vitro biological activity (comparable with or better than cisplatin) against L1210 leukaemia, the corresponding cisplatin resistant line, and a human ovarian cell line, SKOV-3. However, initial in vivo testing against a solid mouse plasmacytoma (PC6) and P388 leukaemia has not revealed significant activity.Katharine A. Smith, Glen B. Deacon, W. Roy Jackson, Edward R. T. Tiekink, Silvina Rainone, and Lorraine K. Webste

Systematic differences in electrochemical reduction of the structurally characterized anti-cancer platinum(IV) complexes [Pt{((p-HC6F4)NCH2)2}-(pyridine)2Cl2], [Pt{((p-HC6F4)NCH2)2}(pyridine)2(OH)2], and [Pt{((p-HC6F4)NCH2)2}(pyridine)2(OH)Cl]

The putative platinum(IV) anticancer drugs, [Pt{((R)NCH(2))(2)}(py)(2)XY] (X,Y=Cl, R=p-HC(6)F(4) (1a), C(6)F(5) (1b); X,Y=OH, R=p-HC(6)F(4) (2); X=Cl, Y=OH, R=p-HC(6)F(4) (3), py = pyridine) have been prepared by oxidation of the Pt(II) anticancer drugs [Pt{((R)NCH(2))(2)}(py)(2)] (R=p-HC(6)F(4) (4a) or C(6)F(5) (4b)) with PhICl(2) (1a,b), H(2)O(2) (2) and PhICl(2)/Bu(4)NOH (3). NMR spectroscopy and the X-ray crystal structures of 1b, 2 and 3 show that they have octahedral stereochemistry with the X,Y ligands in the trans-position. The net two electron electrochemical reduction of 1a, 2 and 3 has been studied by voltammetric, spectroelectrochemical and bulk electrolysis techniques in acetonitrile. NMR and other data reveal that reduction of 1a gives pure 4a via the elimination of both axial chloride ligands. In the case of 2, one end of the diamide ligand is protonated and the resulting -NH(p-HC(6)F(4)) group dissociated giving a [Pt{N(p-HC(6)F(4))CH(2)CH(2)NH(p-HC(6)F(4))}] arrangement, one pyridine ligand is lost and a hydroxide ion retained in the coordination sphere. Intriguingly, in the case of reduction of 3, a 50% mixture of the reduction products of pure 1a and 2 is formed. The relative ease of reduction is 1>3>2. Testing of 1a, 2 and 3 against L1210 and L1210(DDP) (DDP = cis-diamine-dichloroplatinum(II)) mouse leukaemia cells shows all to be cytotoxic with IC(50) values of 1.0-3.5 μM. 2 and 3 are active in vivo against AHDJ/PC6 tumor line when delivered in peanut oil despite being hard to reduce electrochemically, and notably are more active than 4a delivered in this medium whilst comparable with 4a delivered in saline/Tween