- Title
- 1,8-Naphthalimide derivatives: new leads against dynamin i GTPase activity
- Creator
- Abdel-Hamid, Mohammed K.; Macgregor, Kylie A.; Odell, Luke R.; Chau, Ngoc; Mariana, Anna; Whiting, Ainslie; Robinson, Phillip J.; McCluskey, Adam
- Relation
- Organic and Biomolecular Chemistry Vol. 13, Issue 29, p. 8016-8028
- Publisher Link
- http://dx.doi.org/10.1039/c5ob00751h
- Publisher
- Royal Society of Chemistry
- Resource Type
- journal article
- Date
- 2015
- Description
- 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.
- Subject
- dynamin I; Naphthaladyn™; enzyme inhibitors; naphthalimides
- Identifier
- http://hdl.handle.net/1959.13/1316453
- Identifier
- uon:23187
- Identifier
- ISSN:1477-0520
- Language
- eng
- Reviewed
- Hits: 8972
- Visitors: 9359
- Downloads: 2
| Thumbnail | File | Description | Size | Format |
|---|