The reaction products formed by reacting deoxyguanosine with phosphoramide mustard at pH 7.4 have been analyzed by high-performance liquid chromatography and Schiff's reaction. The adducts consisted of five fractions of phosphoramide mustard-imidazole ring-opened deoxyguanosine complexes and one fraction of each of intact phosphoramide mustard-deoxyguanosine and phosphoramide mustard-dideoxygua...

A new cinchona alkaloid derived bifunctional tertiary amine-phosphoramide is identified as a highly enantioselective catalyst for Michael addition of both unprotected 3-arylthio- and 3-alkylthiooxindoles to nitroolefins. The phosphoramide moiety of plays an indispensable role in this reaction.

A series of sulfonyl-group containing analogues of aldophosphamide (Aldo) were synthesized as potential anticancer prodrugs that liberate the cytotoxic phosphoramide mustards (PM, IPM, and tetrakis-PM) via beta-elimination, a nonenzymatic activation mechanism. Kinetic studies demonstrated that all these compounds spontaneously liberate phosphoramide mustards with half-lives in the range of 0.08...

Phosphoramide mustard, an active metabolite of cyclophosphamide, has been reacted separately with guanosine and deoxyguanosine in aqueous solution at pH 7.4. The major adduct which was formed in each case has been isolated by reverse-phase high-pressure liquid chromatography. The structure of the major adduct, as determined by a combination of ultraviolet and field desorption mass spectrometry,...

The systemic use of thiol-containing uroepithelial protecting agents, e.g., N-acetylcysteine (NAC) or mesna, in conjunction with the alkylating agent cyclophosphamide is predicated on the assumption that the toxic metabolic by-products will be consumed by thiol without diminishing the cytotoxicity of the active alkylating intermediate, phosphoramide mustard. Studies in murine tumor systems have...

Phosphoramide mustard-induced DNA interstrand cross-links were studied both in vitro and by computer simulation. The local determinants for the formation of phosphoramide mustard-induced DNA interstrand cross-links were defined by using different pairs of synthetic oligonucleotide duplexes, each of which contained a single potentially cross-linkable site. Phosphoramide mustard was found to cros...

Postimplantation rat embryos (Day 10) were exposed in vitro to teratogenic concentrations of 4-hydroperoxycyclophosphamide, an activated form of cyclophosphamide, and phosphoramide mustard, the major teratogenic metabolite of cyclophosphamide. Following a 5-h exposure to these agents, drug-induced DNA damage was assessed by alkaline elution. Both drugs induced detectable DNA cross-linking at te...

Cyclophosphamide must be metabolically activated to have maximal mutagenic or teratogenic activity. The first step in this activation is hydroxylation to 4-hydroxycyclophosphamide; this metabolite breaks down to form two cytotoxic metabolites, phosphoramide mustard and acrolein. In this report, the mutagenicity and teratogenicity of Cyclophosphamide, 4-hydroperoxycyclophosphamide (which forms 4...

The stability of phosphoramide mustard, a metabolite of cyclophosphamide was studied at pH 7.2 and 37 degrees C using 31P nuclear magnetic resonance. The phosphorus signal of phosphoramide mustard disappeared with a half-life of 8 min indicating rapid conversion to other species. The final product, inorganic phosphate, appeared with a half-life of 105 min indicating that phosphoramide mustard w...

The stability of phosphoramide mustard, a metabolite of cyclophosphamide was studied at pH 7.2 and 37°Cusing 31Pnuclear magnetic resonance. The phosphorus signal of phosphoramide mustard disappeared with a half-life of 8 min indicating rapid conversion to other species. The final product, inorganic phos phate, appeared with a half-life of 105 min indicating that phos phoramide mustard was easi...