Back to Search
Start Over
Development of novel water-soluble photocleavable protective group and its application for design of photoresponsive paclitaxel prodrugs.
- Source :
-
Bioorganic & medicinal chemistry [Bioorg Med Chem] 2008 May 15; Vol. 16 (10), pp. 5389-97. Date of Electronic Publication: 2008 Apr 15. - Publication Year :
- 2008
-
Abstract
- 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 100mgmL(-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 365nm UV light irradiation at low power, while laser activation at 355nm 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.
- Subjects :
- Chromatography, High Pressure Liquid
Coumarins chemistry
Coumarins radiation effects
Lasers
Molecular Conformation
Paclitaxel chemistry
Paclitaxel radiation effects
Photochemistry
Photolysis
Photosensitizing Agents chemistry
Photosensitizing Agents radiation effects
Prodrugs chemistry
Prodrugs radiation effects
Solubility
Stereoisomerism
Ultraviolet Rays
Water chemistry
Coumarins chemical synthesis
Drug Design
Paclitaxel chemical synthesis
Photosensitizing Agents chemical synthesis
Prodrugs chemical synthesis
Subjects
Details
- Language :
- English
- ISSN :
- 1464-3391
- Volume :
- 16
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- Bioorganic & medicinal chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 18440235
- Full Text :
- https://doi.org/10.1016/j.bmc.2008.04.022