Poster Presentations

Start Date

20-5-2014 12:30 PM

Description

A new class of multifunctional small molecule inhibitors of amyloid self-assembly is described. Several compounds, based on the diarylhydrazone scaffold were designed. Forty-four substituted derivatives of this core structure were synthesized using a variety of benzaldehydes and phenylhydrazines and were characterized. The inhibitor candidates were evaluated in multiple assays, including the inhibition of A fibrillogenesis and the disassembly of preformed fibrils. The hydrazone scaffold showed strong activity in inhibiting the amyloid beta self-assembly. The structure-activity relationship revealed that the substituents on the aromatic rings had considerable effect on the overall activity of the compounds. In order to identify possible functional moieties responsible for the strong effect further related compounds (Schiff-bases and their hydrogenated product, secondary amines) were synthesized and tested in the inhibition of fibril formation by Thioflavin-T Fluorescence spectroscopy and the fibril morphology was followed by Atomic Force Microscopy. The data indicated that the N-N linkage appears important while the importance of the conjugation in the inhibitors could not be confirmed.

Comments

Abstract of poster presented at the 2014 UMass Center for Clinical and Translational Science Research Retreat, held on May 20, 2014 at the University of Massachusetts Medical School, Worcester, Mass.

Creative Commons License

Creative Commons Attribution-Noncommercial-Share Alike 3.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial-Share Alike 3.0 License.

Share

COinS
 
May 20th, 12:30 PM

Application of Diarylhydrazones, Schiff-bases and Their Saturated Derivatives as Multifunctional Inhibitors of Amyloid Self-Assembly

A new class of multifunctional small molecule inhibitors of amyloid self-assembly is described. Several compounds, based on the diarylhydrazone scaffold were designed. Forty-four substituted derivatives of this core structure were synthesized using a variety of benzaldehydes and phenylhydrazines and were characterized. The inhibitor candidates were evaluated in multiple assays, including the inhibition of A fibrillogenesis and the disassembly of preformed fibrils. The hydrazone scaffold showed strong activity in inhibiting the amyloid beta self-assembly. The structure-activity relationship revealed that the substituents on the aromatic rings had considerable effect on the overall activity of the compounds. In order to identify possible functional moieties responsible for the strong effect further related compounds (Schiff-bases and their hydrogenated product, secondary amines) were synthesized and tested in the inhibition of fibril formation by Thioflavin-T Fluorescence spectroscopy and the fibril morphology was followed by Atomic Force Microscopy. The data indicated that the N-N linkage appears important while the importance of the conjugation in the inhibitors could not be confirmed.

 

To view the content in your browser, please download Adobe Reader or, alternately,
you may Download the file to your hard drive.

NOTE: The latest versions of Adobe Reader do not support viewing PDF files within Firefox on Mac OS and if you are using a modern (Intel) Mac, there is no official plugin for viewing PDF files within the browser window.