Medizinische Universität Graz - Research portal
Selected Publication:
SHR Neuro Cancer Cardio Lipid Metab Microb
Wang, SR; Yang, CG; Sánchez-Murcia, PA; Snyder, JP; Yan, N; Sáez-Calvo, G; Díaz, JF; Gago, F; Fang, WS.
Restoration of Microtubule Interaction and Cytotoxicity in D-seco Taxanes upon Incorporation of 20-Hydroxymethyl-4-allyloxy Groups.
Org Lett. 2015; 17(24):6098-6101
Doi: 10.1021/acs.orglett.5b03119
Web of Science
PubMed
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- Co-authors Med Uni Graz
- Sánchez Murcia Pedro Alejandro
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- Abstract:
- To probe the exact role of the oxetane D ring in both tubulin binding and cytotoxicity of taxanes, novel D-seco taxanes bearing a C4 ether substituent have been prepared from paclitaxel 1a. Among them, 20-hydroxymethyl-4-allyloxy D-seco taxane 5e is the most active in both tubulin and cytotoxicity assays. It is only slightly less potent than 1a on tubulin polymerization promotion in vitro and the most cytotoxic among all D-seco taxanes known to date. The reason for the loss and restoration of bioactivity for these D-seco taxanes is also discussed with the assistance of NMR and molecular modeling studies. From these results, we draw a conclusion that the intact D ring of taxanes is not strictly necessary for their binding to tubulin and cytotoxic effects.
- Find related publications in this database (using NLM MeSH Indexing)
- Ethers, Cyclic - chemistry
- Microtubules - metabolism
- Models, Molecular -
- Molecular Structure -
- Nuclear Magnetic Resonance, Biomolecular -
- Paclitaxel - chemistry
- Paclitaxel - pharmacology
- Protein Binding -
- Structure-Activity Relationship -