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Issue 29, 2015
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1,8-Naphthalimide derivatives: new leads against dynamin I GTPase activity

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Abstract

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.

Graphical abstract: 1,8-Naphthalimide derivatives: new leads against dynamin I GTPase activity

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Supplementary files

Article information


Submitted
15 Apr 2015
Accepted
11 Jun 2015
First published
16 Jun 2015

Org. Biomol. Chem., 2015,13, 8016-8028
Article type
Paper
Author version available

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

M. K. Abdel-Hamid, K. A. Macgregor, L. R. Odell, N. Chau, A. Mariana, A. Whiting, P. J. Robinson and A. McCluskey, Org. Biomol. Chem., 2015, 13, 8016
DOI: 10.1039/C5OB00751H

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