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Raevsky et al. Neuroimmunol Neuroinflammation 2018;5:33 Neuroimmunology and
DOI: 10.20517/2347-8659.2018.34 Neuroinflammation

Original Article Open Access

In silico design of novel gold-phosphate containing
compounds as selective inhibitors of cathepsin B in
neuroinflammation

Alexsey V. Raevsky , Mohsen Sharifi , Vasily Pinchuk , Andis Klegeris 5
4
1
2,3
1 Laboratory of Structural Biology, Institute of Food Biotechnology and Genomics, National Academy of Sciences of Ukraine, Kyiv 04123,
Ukraine.
2 Medway School of Pharmacy, Universities of Kent and Greenwich, Kent ME4 4TB, UK.
3 Division of Systems Biology, National Center for Toxicological Research, US Food and Drug Administration, Jefferson, AR 72079, USA.
4 Life Chemicals Ltd., Niagara-on-the-Lake, ON L0S 1J0, Canada.
5 Department of Biology, University of British Columbia, Okanagan Campus, Kelowna, BC V1V 1V7, Canada.
Correspondence to: Dr. Alexsey V. Raevsky, Laboratory of Structural Biology, Institute of Food Biotechnology and Genomics, National
Academy of Sciences of Ukraine, Kyiv 04123, Ukraine. Email: o.v.raievskyi@imbg.org.ua; Dr. Andis Klegeris, Department of Biology,
University of British Columbia, Okanagan Campus, Kelowna, BC V1V 1V7, Canada. E-mail: andis.klegeris@ubc.ca

How to cite this article: Raevsky AV, Sharifi M, Pinchuk V, Klegeris A. In silico design of novel gold-phosphate containing compounds
as selective inhibitors of cathepsin B in neuroinflammation. Neuroimmunol Neuroinflammation 2018;5:33.
http://dx.doi.org/10.20517/2347-8659.2018.34
Received: 8 Jun 2018 First Decision: 25 Jul 2018 Revised: 31 Jul 2018 Accepted: 31 Jul 2018 Published: 27 Aug 2018

Science Editor: Athanassios P. Kyritsis Copy Editor: Jun-Yao Li Production Editor: Huan-Liang Wu

ABSTRACT
Aim: Alzheimer’s disease is characterized by pathological protein aggregates and microglia-driven chronic
neuroinflammation. Cathepsin B has been proposed as the potential target for inhibiting adverse activation of
microglia and slowing down this neurodegenerative disease. Currently available inhibitors of cathepsin B enzymatic
activity are non-selective; therefore, the design and synthesis of novel specific inhibitors could facilitate the
development of a new class of anti-Alzheimer medications targeting the neuroinflammatory component of this
disease.

Methods: We describe molecular design strategies, which were used to create specific cathepsin B inhibitors based
on the structure of the gold-containing drug auranofin (Ridaura), and its covalent binding to the cysteine residue of
the active site of cathepsins.

Results: This in silico study investigated the structure-activity relationship of a series of newly designed derivatives
of auranofin with regard to their cathepsin B inhibitory activity. An exhaustive molecular screening model was
designed and validated by using a set of known cathepsin B inhibitors. Its validity was further tested during

© The Author(s) 2018. Open Access This article is licensed under a Creative Commons Attribution 4.0
International License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use,
sharing, adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as long
as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license,
and indicate if changes were made.

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