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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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Publication details

The article was received on 15 Apr 2015, accepted on 11 Jun 2015 and first published on 16 Jun 2015


Article type: Paper
DOI: 10.1039/C5OB00751H
Author version available: Download Author version (PDF)
Citation: Org. Biomol. Chem., 2015,13, 8016-8028
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    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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