1,8-Naphthalimide derivatives: new leads against dynamin i GTPase activity

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 (IC_50(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
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