Activated cyclophosphamides such as 4-sulfoethylthiocyclophosphamide (mafosfamide) are suitable for a local intracavitary chemotherapy, whereas cyclophosphamide requires a metabolic activation. Mafosfamide administered i.p. in mice was less toxic (50% lethal dose, 640 mg/kg) than its i.v. application (50% lethal dose, 480 mg/kg). A further remarkable reduction of toxicity with an increase of th...

Detoxification of cyclophosphamide is effected, in part, by hepatic class 1 aldehyde dehydrogenase (ALDH-1)-catalyzed oxidation of aldophosphamide, a pivotal aldehyde intermediate, to the nontoxic metabolite, carboxyphosphamide. This enzyme is found in erythrocytes as well. Detoxification of aldophosphamide may also be effected by enzymes, viz. certain aldo-keto reductases, that catalyze the re...

“Il Principe” (the Prince) is the nickname given to a spectacular Mid Upper Palaeolithic (Gravettian) burial discovered at Arene Candide, Italy in 1942. Arene Candide is a large cave located about 90 m above sea level on the slope of the Caprazoppa promontory, along the Ligurian coast near Finale Ligure (Savona, Italy). The cave is named after a dune of white siliceous sand of aeolian origin, b...

Several mouse aldehyde dehydrogenases catalyze the detoxification of aldophosphamide, the pivotal metabolite of the prodrugs cyclophosphamide, mafosfamide, and other oxazaphosphorines. N-Isopropyl-p-formylbenzamide, a major metabolite of procarbazine, was found to be an excellent substrate (Km = 0.84 microM) for at least one of these enzymes, namely, mouse aldehyde dehydrogenase-2. The Km for m...

The R2PI-TOF spectra of supersonically expanded rare gas/chiral arene heteroclusters have been rationalized in terms of the distortion of the pi-electron density reflecting the different dipole and quadrupole momenta induced in the rare gas atoms by interaction with the opposite pi-faces of the chiral arene itself.

Reduction of [U(Ts(Tol))(Cl)(μ-Cl)U(Ts(Tol))(THF)2] [2, Ts(Tol) = HC(SiMe2NAr')3; Ar' = 4-MeC6H4)] with KC8 in toluene afforded the new arene-bridged diuranium complex [{U(Ts(Tol))}2(μ-η(6):η(6)-C6H5Me)] (3); combined structural, spectroscopic, magnetic, and computational analyses unambiguously confirm that the uranium centres in 3 are in the +5 oxidation state and the toluene is a 10π-tetraanion.

According to general doctrine [1] canceroselectivity of Cyclophosphamide is based on different activities of the 4hydroxycyclophosphamide (OHCP) detoxifying cellular enzyme aldehyde dehydrogenase in tumor and normal cells. Aldehyde dehydrogenase converts the OHCP tautomere aldophosphamide (ALDO) to the non-cytotoxic carboxyphosphamide. Due to different activities of the detoxifying enzyme more ...