Enhanced Hydrolytic Stability and Water Solubility of an Aromatic Nitrogen Mustard by Conjugation with Molecular Umbrellas
- 29 March 2003
- journal article
- Published by American Chemical Society (ACS) in Bioconjugate Chemistry
- Vol. 14 (3), 667-671
- https://doi.org/10.1021/bc034007s
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.Keywords
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