Anticancer drugs, separation

In order to put the MDR substrates in their medical and pharmacological context, we present some of the key molecules in separate figures. Figure 3 shows anticancer drugs, which are, unfortunately for the patients, also MDR substrates. Figure 4 shows the chemical MDR modulators used experimen-... 

One attraction of SHW is that it can be used for reversed-phase separations and is therefore readily applicable to a wide range of pharmaceutical compounds including barbiturates, sulfonamides, analgesics and steroids (Table 18-2), and anticancer drugs, including 5-fluorouracil, methotrexate, and... 

Figure 18-11. Separation of the anticancer drugs 5-fluorouracil (5-FU), methotrexate (MTX), 7-hydroxymethotrexate (7-OH-MTX), and etopoxide (VP-16) using superheated water and a PS-DVB column at 80°C. (Reproduced from reference 75, with permission. Copyright 2001, American Chemical Society.)...

T. Teutenberg, O. Lerch. H-J. Gotze, and P. Zinn, Separation of selected anticancer drugs using superheated water as the mobile phase, Anal. Chem. 73 (2001), 3896-3899. 

Taxus (yew) trees contain alkaloids called taxanes that have anticancer activity and are the basis of the semisynthetic anticancer drugs paclitaxel and docetaxel (see separate monographs), which are based on taxol, from Taxus brevifolia. 

Because microtubules are required for the separation of chromosomes along the spindle in mitosis, drugs that interfere with microtubule polymerization and depolymerization can be used to selectively attack cells that are in mitosis. This is one of the strategies used to treat cancer, and drugs such as vinblastine and vincristine, which disrupt spindle microtubules, or taxol, which stabilizes microtubules, are used as anticancer drugs. 

The HD AC family of proteins plays a critical role in modulating chromatin structure and in regulating the functions of other proteins. Several HDAC inhibitors are used in clinical trials as anticancer drugs. However, these inhibitors are not selective among the multiple HDAC paralogs that have been identified. Thus, new selective inhibitors are required to separate the functions of the various HDAC family members. In particular, treatment with pan-HDAC inhibitors also results in hyperacetylation of a-tubulin, the functional implications of which are unclear. 

Two isoflavanoids and one triterpenoid (formononetin, isoliquiritigenin, 18-) -glycynfaetinic acid) were used as compliance marker compounds for a patient on an anticancer drug extracted from licorice roots [367]. A C j column (particle beam MS) and a rapid I-min gradient from 40/55/5 to 95/0/5 methanol/water/fOTmic acid (hold 10 min) generated the separation. 

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