The Rhodadyns, a New Class of Small Molecule Inhibitors of Dynamin GTPase Activity - PubMed (original) (raw)

. 2012 Mar 26;3(5):352-6.

doi: 10.1021/ml200284s. eCollection 2012 May 10.

Gordana Hadzic 1, Joseph Ambrus 1, D Yuri Pomè 1, Emily Hyde 1, Ainslie Whiting 2, Anna Mariana 2, Lisa von Kleist 3, Ngoc Chau 2, Volker Haucke 3, Phillip J Robinson 2, Adam McCluskey 1

Affiliations

The Rhodadyns, a New Class of Small Molecule Inhibitors of Dynamin GTPase Activity

Mark J Robertson et al. ACS Med Chem Lett. 2012.

Abstract

Six focused rhodanine-based libraries, 60 compounds in total, were synthesized and evaluated as potential dynamin I GTPase inhibitors. Twenty-six were more potent than the lead compound with 13 returning IC50 values ≤10 μM, making the Rhodadyn series among the most active dynamin inhibitors reported. Two analogues were highly effective at blocking receptor-mediated endocytosis: C10 and D10 with IC50(RME) = 7.0 ± 2.2 and 5.9 ± 1.0 μM, respectively. These compounds are equipotent with the best reported in-cell dynamin inhibitors.

Keywords: Knoevengal condensation; dynamin inhibition; rhodanine.

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Figures

Figure 1

Figure 1

Chemical structure of the lead Rhodadyn A1.

Figure 2

Figure 2

(a) Rhodanines (A–F) and (b) aldehydes (1–10) used in the synthesis of libraries A–F.

Scheme 1

Scheme 1

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