Development of novel water-soluble photocleavable protective group and its application for design of photoresponsive paclitaxel prodrugs

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• 作者：Mayo Noguchi ; Mariusz Skwarczynski ; Halan Prakash ; Shun Hirota ; Tooru Kimura ; Yoshio Hayashi ; Yoshiaki Kiso
• 关键词：Water-soluble photocleavable protective group ; Prodrug of paclitaxel ; Taxol ; O– ; N intramolecular acyl migration
• 刊名：Bioorganic and Medicinal Chemistry
• 出版年：2008
• 出版时间：15 May 2008
• 年：2008
• 卷：16
• 期：10
• 页码：5389-5397
• 全文大小：464 K

文摘

A novel coumarin-based highly water-soluble photocleavable protective group was designed and synthesized, and then this photosensitive protecting group was used to design paclitaxel prodrugs. These novel paclitaxel conjugates demonstrated excellent water solubility, over 100 mg mL⁻¹. Thus, the use of a detergent in the formulation can be omitted completely, even at high doses. Phototaxel 11 released the parent drug, paclitaxel, quickly and efficiently by minimal tissue-damaging 365 nm UV light irradiation at low power, while laser activation at 355 nm led to extensive decomposition of the prodrug. The carbamate-type prodrug, phototaxel 11, was stable in the dark prior to activation, whereas carbonate-type phototaxel 9 demonstrated poor stability under aqueous conditions. For such prodrugs, tumor-tissue targeting after administration could be achieved by selective light delivery, similar to that used in photodynamic therapy. In addition, newly designed coumarin derivative 8 can be applied in organic chemistry as a photosensitive protective group and for the design of caged compounds.