A comparison of multifunctional donors of carbon monoxide: Their anticoagulant, antioxidant, anti-aggregatory and cytotoxicity activities in an in vitro model.

The study examines the effect of two water-soluble carbon monoxide (CO) donors, CORM-3 and CORM-A1, on selected parameters of oxidative stress and hemostasis in human plasma and blood platelets in vitro. It also compares their activity with that of the lipid-soluble CORM-2. The oxidation of amino acid residues in plasma proteins was evaluated by measuring the amounts of thiol and carbonyl groups. Plasma lipid peroxidation was measured as thiobarbituric acid reactive substance (TBARS) concentration. In addition, three haemostatic parameters of plasma were studied, viz. activated partial thromboplastin time (APTT), prothrombin time (PT) and thrombin time (TT), and one haemostatic parameter of platelets (platelet aggregation). Treatment with CORM-3 and CORM-A1 (all concentrations from 0.1 to 100 µM) decreased thiol group oxidation induced by H2O2/Fe. Incubation with CORM-3 and CORM-A1 also influenced plasma coagulation activity, e.g. CORM-3 and CORM-A1 significantly prolonged TT at the two highest tested concentrations (50 and 100 µM). Only CORM-2 at the highest tested concentration (100 µM) and CORM-3 (50 and 100 µM) reduced platelet aggregation induced by ADP. None of the tested CORMs caused platelet damage. The treatment of various diseases associated with oxidative stress, including cardiovascular diseases, may be enhanced by the administration of CO donors CORM-2 and CORM-3, these being modulators of oxidative stress and hemostasis.

Synthesis and tumor-uptake study of phosphate esters of polyhedral hydroxyboranes.

The phosphorylations of B12H11OH2-,B12H10(OH)2-2-, and B20H17OH4-with POCl3 and (C6H5O)2POCl were investigated and the following derivatives were isolated: B12H11OPO3H3-,B12H11OPO3H2-2-,B12H11OPO(OC6H5)-2-2 minus, B12H11OPO(OC6H5)OH2 minus, b12h10(op2o6h2)2-4 minus, B12H10(OPO3H2)2-2 minus, B12Br10(OPO3H)2-4 minus, B12H10[O-PO(OC6H5)2]2-2 minus, B20H18OP2O6H2-4 minus, B20H18OPO3H2-3 minus. The B-O-P bonds proved very resistant to hydrolysis and the phosphates were administered in the for of Na+ salts at pH 7.2 to rats bearing subcutaneous glioma. The boron concentrations in tumors and the tumor/blood concentration ratios were compared with those of parent hydroxy derivatives. Except when the POH function was blocked by phenyl groups the phosphorylation invariably resulted in a greatly enhanced uptake of the borane into tumors and improved the tumor/blood boron ratio. The phopshate function appears to be one of the most effective handles for the incorporation of boron into brain tumors and the compounds show considerable promise for use in the neutron capture therapy of brain tumors.