A focused library of TX-67 (C10 hemi-succinate) analogs have been prepared including regioisomeric, functional group, and
one-carbon homologs. These were prepared to investigate TX-67’s lack of interaction with P-glycoprotein (Pgp). Tubulin stabilization
ability, cytotoxicity, and Pgp interactions were evaluated. All carboxylic acid analogs had no apparent interactions with Pgp whereas the
ester variants of the same compounds displayed characteristics of Pgp substrates. Furthermore, it is demonstrated that hydrogen-bonding
properties were significant with respect to Pgp interactions. This anionic introduction strategy may allow for delivery of paclitaxel into
the CNS as well as establishing a new method for delivery of other, non-CNS permeable drugs.
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