Suzy Cros

Platinum and palladium complexes of 3-methyl orotic acid: a route toward palladium complexes with good antitumor activity.

In order to design and develop potential anticancer drugs involving the same structural pattern as platinum(II) antitumor complexes, complexes of palladium and platinum with 3-methyl-orotic acid as the leaving ligand have been synthesized. The study of the anticancer activity of these compounds toward L1210 leukemia and sarcoma 180 in mice is presented and discussed in terms of the nature of the ligand and the metal involved. The (3-methylorotato)(1,2-diamino-cyclohexane) palladium(II) has an activity (sarcoma 180) similar to that for cis-DDP itself. The crystal structure of (3-methylorotato)(dl-trans-1,2-diaminocyclohexane) platinum(II) is described.

Antitumour activity of some cyclophosphazenes

Abstract Among six cyclophosphazenes tested for antitumour activity against mouse P388, L1210 and B16 tumours respectively, activity was shown by the hexaziridinocyclotriphosphazene (N3P3Az6; all three tumours), the octaziridinocyclotetraphosphazene (N4P4Az8; all three tumours) and the octapyrrolidinocyclotetraphosphazene (N4P4Pyrro8; P388 tumour). The most effective in each case is the hexaziridino trimer compound, N3P3Az6, which has the advantage of high water solubility and activity both by the i.v. and by the i.p. route. Three compounds, N3P3Cl6, N4P4Cl8 and N3P3Pyrro6 were inactive. The mode of action of these drugs on DNA and a possible structure-activity relationship are briefly discussed.

New designs in inorganic ring systems as anticancer drugs. Antitumor activity of the aziridino (ethyleneimino) derivatives (NPAz2)2NSOX with X = F, Az, Ph

Abstract As a result of a preliminary screening, 3 aziridino (ethylene-imino) derivatives of the thiatriazadiphosphorine ring system with formula (NPAz2)2NSOX (X = F, Az, Ph) were found to exhibit significant antitumor activity. Experiments in vivo were carried out on P388 and L1210 leukemias in female DBA 2 mice and on B16 melanoma in female C57 black mice. Both the toxicity and the antitumor activity are to a large extent determined by the sulphur-bonded group X.

In vivo evidence of complete circumvention of vincristine resistance by a new triazinoaminopiperidine derivative S 9788 in P388/VCR leukemia model

SummaryS 9788, a new triazinoaminopiperidine derivative, was found to be a potent reversant of vincristine resistance in the in vivo murine leukemic P388/VCR model. In two treatment regimens (Q4D days 1, 5 and 9 and QD days 1–9), S 9788 enhanced the antitumor activity of vincristine in a dose-dependent manner, resulting in a complete circumvention of drug resistance for well-tolerated doses of S 9788. S 9788 was also effective in enhancing therapeutic effects of vincristine in the treatment of sensitive P388-bearing mice. These results strongly suggest that S 9788 may be a potential candidate for circumvention of multidrug resistance (MDR) in clinical practice.

Cytotoxic hybrid molecules ‘metalloporphyrin–ellipticine’ having a high affinity for DNA

Hybrid molecules ‘cationic metalloporphyrin–intercalators’ have been synthesized which have a high affinity for double-stranded DNA and are able to cleave it at low concentrations; compound (2), an efficient bleomycin model based on a cationic metalloporphyrin, is cytotoxic towards murine leukaemia cells L1210 in vitro; iron and zinc analogues of (2) are less active, despite having the same affinity for nucleic acids.

Synthesis and in vitro cytotoxicity of diastereoisomerically modified dolastatin 15 analogues

Dolastatin 15 1(4S,7S) is a potent cytostatic depsipeptide of marine origin. Analysis of the effects of the stereochemistry in the non-peptide moiety on activity revealed that chirality inversion in the aromatic terminal region preserves the antiproliferative activity.

Comparison (nature and biological activity) between two new blue species involving, respectively, malonamide and succinamic acid as ligands

Abstract Although the preparation of blue platinum complexes is generally achieved through the reaction of a ligand involving a HNCS group with the hydrolysis products of cis -Pt(NH 3 ) 2 Cl 2 , blue species may be obtained using M 2 PtCl 4 as platinum precursors. Two new blue species involving malonamide and succinamic acid have been prepared according to this process. They display the main characteristics of the blue species, i.e. : an absorption near 660 nm in their visible spectrum, a paramagnetic behaviour (EPR signal and platinum atoms in a nonintegral oxidation state. In both cases, solid state infrared spectroscopy gives evidence of coordination through the deprotonated amido groups. The two species have been tested for antitumor activity and toxicity using Sarcoma 180 in mice. Examination of test data shows important differences between the two compounds. For instance, malonamide blue does not significantly improve the median survival time (T/C) at doses up to 1100 mg/Kg body w. while a single dose (150 mg/Kg) of the succinamic acid species produces a 189% T/C (10% survivors). The analytical data and the physico-chemical properties of the two blue species are considered with the aim of suggesting likely explanations of the differences observed in their biological properties.