title: Enhanced hydrolytic stability and water solubility of an aromatic nitrogen mustard by conjugation with molecular umbrellas.
abstract: Chlorambucil, an aromatic nitrogen mustard, has been conjugated to putrescine- and spermidine-based scaffolds bearing one, two, and four persulfated cholic acid units. Those conjugates bearing two or four sterols show improved hydrolytic stability and water solubility relative to chlorambucil. A similar conjugate that contained only one sterol unit shows negligible improvement in hydrolytic stability but a significant increase in water solubility. Qualitatively, the hydrolytic stability within this series of conjugates parallels the shielding effects that have previously been found for related conjugates bearing a pendant, hydrophobic fluorescent probe. In vitro studies indicate that these conjugates possess modest to moderate activity against certain human lymphoblastic leukemia and human colon carcinoma cells.
authors.affiliation: Department of Chemistry, Lehigh University, Bethlehem, Pennsylvania 18015, USA.
authors.forename: Saketh
authors.initials: S
authors.lastname: Vijayaraghavan
authors.forename: Bingwen
authors.initials: B
authors.lastname: Jing
authors.forename: Tracy
authors.initials: T
authors.lastname: Vrablik
authors.forename: Ting-Chao
authors.initials: TC
authors.lastname: Chou
authors.forename: Steven L
authors.initials: SL
authors.lastname: Regen
mesh_terms: D045744:Cell Line, Tumor / Q000187:drug effects; D002699:Chlorambucil / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D004355:Drug Stability; D006801:Humans; D006868:Hydrolysis; D009588:Nitrogen Mustard Compounds / Q000737:chemistry* / Q000378:metabolism* / Q000494:pharmacology; D012995:Solubility; D014867:Water / Q000737:chemistry
chemical_list: D009588:Nitrogen Mustard Compounds; D014867:Water; D002699:Chlorambucil