دورية أكاديمية
New indolesulfonamide derivatives targeting the colchicine site of tubulin: synthesis, anti-tumour activity, structure–activity relationships, and molecular modelling
| العنوان: | New indolesulfonamide derivatives targeting the colchicine site of tubulin: synthesis, anti-tumour activity, structure–activity relationships, and molecular modelling |
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| المؤلفون: | Alba Vicente-Blázquez, Myriam González, Manuel Medarde, Faustino Mollinedo, Rafael Peláez |
| المصدر: | Journal of Enzyme Inhibition and Medicinal Chemistry, Vol 36, Iss 1, Pp 2025-2044 (2021) |
| بيانات النشر: | Taylor & Francis Group, 2021. |
| سنة النشر: | 2021 |
| المجموعة: | LCC:Therapeutics. Pharmacology |
| مصطلحات موضوعية: | indolesulfonamides, antimitotic, total polar surface area, structure–activity relationships, colchicine-site, Therapeutics. Pharmacology, RM1-950 |
| الوصف: | Searching for improved indolesulfonamides with higher polarities, 45 new analogues with modifications on the sulfonamide nitrogen, the methoxyaniline, and/or the indole 3-position were synthesised. They show submicromolar to nanomolar antiproliferative IC50 values against four human tumour cell lines and they are not P-glycoprotein substrates as their potencies against HeLa cells did not improve upon cotreatment with multidrug resistance (MDR) inhibitors. The compounds inhibit tubulin polymerisation in vitro and in cells, thus causing a mitotic arrest followed by apoptosis as shown by cell cycle distribution studies. Molecular modelling studies indicate binding at the colchicine site. Methylated sulfonamides were more potent than those with large and polar substitutions. Amide, formyl, or nitrile groups at the indole 3-position provided drug-like properties for reduced toxicity, with Polar Surface Areas (PSA) above a desirable 75 Å2. Nitriles 15 and 16 are potent polar analogues and represent an interesting class of new antimitotics. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 1475-6366 1475-6374 14756366 |
| العلاقة: | https://doaj.org/toc/1475-6366Test; https://doaj.org/toc/1475-6374Test |
| DOI: | 10.1080/14756366.2021.1975277 |
| الوصول الحر: | https://doaj.org/article/4440c403bfdf45ff83923cb608fc398cTest |
| رقم الانضمام: | edsdoj.4440c403bfdf45ff83923cb608fc398c |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 14756366 14756374 |
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| DOI: | 10.1080/14756366.2021.1975277 |