Degradants TAXOL

Taxol (paclitaxel) is a cytotoxic drug that has been shown to have potent antileukemic and tumor inhibitory properties. Taxol suffers from very poor water solubility (0.25 pg/mL), and hence, a few phosphate ester prodrugs of taxol have been synthesized. While great improvement of water solubility was achieved (>10 mg/mL), these prodrugs were resistant to degradation by alkaline phosphatase, probably due to hindered enzyme access, and no free taxol was formed [50],... 

Liquid chromatography thermospray—mass spectrometry has been utilized to determine the identity and purity of taxol, solvent-induced degradation of cloxacillin [129], benzodiazepines, and ethanolamine-type antihistamines [130]. Electrospray LC-MS has been used for peptide mapping of the human growth hormone [131]. 

Waugh, W.N. Trissel, L.A. Stella, V.J. Stability, compatibility, and plasticizer extraction of taxol (NSC-125973) injection diluted in infusion solutions and stored in various containers. Am.J.Hosp.Pharm., 1991, 48, 1520-1524 [stability-indicating simultaneous degradation products injections 5% dextrose saline]... 

Most studies of structure activity relationships (SAR) rely on degradations of baccatin and semisynthesis. [1, 3, 4] First insights into the SAR of taxol derivatives have been summerized in a recent article on C ring aryl derivatives, [4] and more can be expected in the near future as patented information becomes released. Total synthesis, especially in preparing the way for the synthesis of derivatives, will be of great importance to elucidate the relationship between structure, microtubuli stabilization and anticancer activity more thoroughly. This impact of total syn-... 

Nicolaou KC, Nantermet PG, Ueno H, Guy RK, Couladouros EA, Sorensen EJ (1995) Total Synthesis of Taxol. 1. Retrosynthesis, Degradation, and Reconstitution. J Am Chem Soc 117 624... 

The current clinical formulation of anti-cancer drug taxol is in a 50 50 mixture of Cremophore EL and ethanol, which is physically incompatible with intravenous infusion system and causes serious side effects such as hypersensitivity and neurotoxicity. (31) Here, degradable OCL worm micelles prove to be compatible with cultured cells and blood, offering great advantage over the conventionally surfactants as a potential alternative carrier for taxol. 

Figure 7. Release profiles of taxol from (a) OCLl and (b) OCL3 worm micelles in pH 5 Hepes(%) and pH 7 PBS buffers (M) at 37 XlJnsets are the corresponding degradation-induced OCL worm micelle contour length shortening with time.

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