| Autor: |
Abdel-Hamid MK; Centre for Chemical Biology, Chemistry, School of Environmental and Life Sciences, The University of Newcastle, Callaghan, NSW 2308, Australia. Adam.McCluskey@newcastle.edu.au., Macgregor KA, Odell LR, Chau N, Mariana A, Whiting A, Robinson PJ, McCluskey A |
| Jazyk: |
angličtina |
| Zdroj: |
Organic & biomolecular chemistry [Org Biomol Chem] 2015 Aug 07; Vol. 13 (29), pp. 8016-28. Date of Electronic Publication: 2015 Jun 29. |
| DOI: |
10.1039/c5ob00751h |
| Abstrakt: |
Fragment-based in silico screening against dynamin I (dynI) GTPase activity identified the 1,8-naphthalimide framework as a potential scaffold for the design of new inhibitors targeting the GTP binding pocket of dynI. Structure-based design, synthesis and subsequent optimization resulted in the development of a library of 1,8-naphthalimide derivatives, called the Naphthaladyn™ series, with compounds 23 and 29 being the most active (IC50 of 19.1 ± 0.3 and 18.5 ± 1.7 μM respectively). Compound 29 showed effective inhibition of clathrin-mediated endocytosis (IC50(CME) 66 μM). The results introduce 29 as an optimised GTP-competitive lead Naphthaladyn™ compound for the further development of naphthalimide-based dynI GTPase inhibitors. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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