Novel Purine-Based Fluoroaryl-1,2,3-triazoles as Neuroprotecting Agents: Synthesis, Neuronal Cell Culture Investigations, and CDK5 Docking Studies

Abstract

A series of novel purine-based fluoroaryl triazoles were synthesized using the Cu(I) catalyzed 1,3-dipolar cycloaddition reactions (click reactions), and assayed for their neuroprotective effects using fluorescence electron microscopy. Among these triazoles, o-fluorophenylmetyl-triazole, 7, has comparable neuroprotective effect as that of Flavopiridol (1) and Roscovitine (2), the state of the art CDK inhibitors, against the Aß induced neurotoxicity. These results are substantiated using computer docking methods (DarwinDock/GenDock), which predict that Roscovitine and the triazole 7 bind to the ATP-binding site of CDK5/p25 with comparable binding energies, whereas the corresponding pentafluorophenylmethyl-triazole, 9, has dramatically reduced binding energy (in accordance with its lack of neuroprotection). These combined experimental and theoretical studies support the involvement of CDK5/p25 in the neuronal cell cycle re-entry.

Department(s)

Chemistry

Comments

This article is corrected by an erratum.

Keywords and Phrases

ATP; CDK5; Cell cycle inhibitors; Docking methods; Flavopiridol; Neuroprotectors; Purine triazoles; Roscovitine

International Standard Serial Number (ISSN)

0960-894X

Document Type

Article - Journal

Document Version

Citation

File Type

text

Language(s)

English

Rights

© 2011 Elsevier, All rights reserved.

Publication Date

01 Jul 2011

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