Academic Journal
Quinolin-6-Yloxyacetamides Are Microtubule Destabilizing Agents That Bind to the Colchicine Site of Tubulin
| العنوان: | Quinolin-6-Yloxyacetamides Are Microtubule Destabilizing Agents That Bind to the Colchicine Site of Tubulin |
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| المؤلفون: | Ashwani Sharma, Gonzalo Sáez-Calvo, Natacha Olieric, Francisco de Asís Balaguer, Isabel Barasoain, Clemens Lamberth, J. Fernando Díaz, Michel O. Steinmetz |
| المصدر: | International Journal of Molecular Sciences, Vol 18, Iss 7, p 1336 (2017) |
| بيانات النشر: | MDPI AG |
| سنة النشر: | 2017 |
| المجموعة: | Directory of Open Access Journals: DOAJ Articles |
| مصطلحات موضوعية: | microtubules, microtubule targeting agents, quinolin-6-yloxyacetamides, multidrug resistance, Biology (General), QH301-705.5, Chemistry, QD1-999 |
| الوصف: | Quinolin-6-yloxyacetamides (QAs) are a chemical class of tubulin polymerization inhibitors that were initially identified as fungicides. Here, we report that QAs are potent anti-proliferative agents against human cancer cells including ones that are drug-resistant. QAs act by disrupting the microtubule cytoskeleton and by causing severe mitotic defects. We further demonstrate that QAs inhibit tubulin polymerization in vitro. The high resolution crystal structure of the tubulin-QA complex revealed that QAs bind to the colchicine site on tubulin, which is targeted by microtubule-destabilizing agents such as colchicine and nocodazole. Together, our data establish QAs as colchicine-site ligands and explain the molecular mechanism of microtubule destabilization by this class of compounds. They further extend our structural knowledge on antitubulin agents and thus should aid in the development of new strategies for the rational design of ligands against multidrug-resistant cancer cells. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 1422-0067 |
| Relation: | http://www.mdpi.com/1422-0067/18/7/1336; https://doaj.org/toc/1422-0067; https://doaj.org/article/47fcb6bcfe27420a98af2cc452b326f6 |
| DOI: | 10.3390/ijms18071336 |
| الاتاحة: | https://doi.org/10.3390/ijms18071336 https://doaj.org/article/47fcb6bcfe27420a98af2cc452b326f6 |
| رقم الانضمام: | edsbas.18F9DE3E |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 14220067 |
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| DOI: | 10.3390/ijms18071336 |