Journal
JOURNAL OF MEDICINAL CHEMISTRY
Volume 57, Issue 22, Pages 9554-9563Publisher
AMER CHEMICAL SOC
DOI: 10.1021/jm501276u
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Funding
- National Cancer Institute of the National Institutes of Health [R01-CA168365]
- University of Maryland
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We studied the influence of the aromatic sidewalls on the ability of acyclic CB[n]-type molecular containers (1a1e) to act as solubilizing agents for 19 insoluble drugs including the developmental anticancer agent PBS-1086. All five containers exhibit good water solubility and weak self-association (K-s = 624 M-1). We constructed phase solubility diagrams to extract K-sl and K-a values for the container drug complexes. The acyclic CB[n]-type containers generally display significantly higher K-a values than HP-beta-CD toward drugs. Containers 1a1e bind the steroidal ring system and aromatic moieties of insoluble drugs. Compound 1b displays highest affinity toward most of the drugs studied. Containers 1a and 1b are broadly applicable and can be used to formulate a wider variety of insoluble drugs than was previously possible with cyclodextrin technology. For drugs that are solubilized by both HP-beta-CD and 1a1e, lower concentrations of 1a1e are required to achieve identical [drug].
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