CaltechAUTHORS
  A Caltech Library Service

Novel purine-based fluoroaryl-1,2,3-triazoles as neuroprotecting agents: Synthesis, neuronal cell culture investigations, and CDK5 docking studies

Nair, Nanditha and Kudo, Wataru and Smith, Mark A. and Abrol, Ravinder and Goddard, William A., III and Reddy, V. Prakash (2011) Novel purine-based fluoroaryl-1,2,3-triazoles as neuroprotecting agents: Synthesis, neuronal cell culture investigations, and CDK5 docking studies. Bioorganic and Medicinal Chemistry Letters, 21 (13). pp. 3957-3961. ISSN 0960-894X. https://resolver.caltech.edu/CaltechAUTHORS:20110627-112305378

[img] MS Word (Computational methodology, neuronal cytotoxicity studies, and synthesis of compounds.) - Supplemental Material
See Usage Policy.

64Kb
[img]
Preview
PDF - Erratum
See Usage Policy.

112Kb

Use this Persistent URL to link to this item: https://resolver.caltech.edu/CaltechAUTHORS:20110627-112305378

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 Aβ 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.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1016/j.bmcl.2011.05.019DOIArticle
http://www.sciencedirect.com/science/article/pii/S0960894X11006482PublisherArticle
ORCID:
AuthorORCID
Abrol, Ravinder0000-0001-7333-6793
Goddard, William A., III0000-0003-0097-5716
Additional Information:© 2011 Elsevier Ltd. Received 10 April 2011; revised 5 May 2011; accepted 6 May 2011. Available online 14 May 2011.
Subject Keywords:CDK5; Docking methods; ATP; Roscovitine; Flavopiridol; Purine triazoles; Cell cycle inhibitors; Neuroprotectors
Issue or Number:13
Record Number:CaltechAUTHORS:20110627-112305378
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20110627-112305378
Official Citation:Nanditha Nair, Wataru Kudo, Mark A. Smith, Ravinder Abrol, William A. Goddard III, V. Prakash Reddy, Novel purine-based fluoroaryl-1,2,3-triazoles as neuroprotecting agents: Synthesis, neuronal cell culture investigations, and CDK5 docking studies, Bioorganic & Medicinal Chemistry Letters, Volume 21, Issue 13, 1 July 2011, Pages 3957-3961, ISSN 0960-894X, DOI: 10.1016/j.bmcl.2011.05.019.
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:24224
Collection:CaltechAUTHORS
Deposited By: Jason Perez
Deposited On:27 Jun 2011 20:34
Last Modified:03 Oct 2019 02:54

Repository Staff Only: item control page