Enhanced hydrolytic stability and water solubility of an aromatic nitrogen mustard by conjugation with molecular umbrellas.
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.
Vijayaraghavan
Saketh
S
Department of Chemistry, Lehigh University, Bethlehem, Pennsylvania 18015, USA.
Jing
Bingwen
B
Vrablik
Tracy
T
Chou
Ting-Chao
TC
Regen
Steven L
SL
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
D009588:Nitrogen Mustard Compounds; D014867:Water; D002699:Chlorambucil