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Pharmaceuticals
Volume 11
Issue 1
10.3390/ph11010022
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Article

A Novel Interaction Between the TLR7 and a Colchicine Derivative Revealed Through a Computational and Experimental Study

by
Francesco Gentile
1,
Marco A. Deriu
2,
Khaled Barakat
3,
Andrea Danani
2 and
Jack Tuszynski
1,4,5,*
1
Department of Physics, University of Alberta, AB T6G 2E1 Edmonton, Canada
2
Istituto Dalle Molle di Studi Sull’intelligenza Artificiale (IDSIA), Scuola Universitaria Professionale della Svizzera Italiana (SUPSI), Università della Svizzera Italiana (USI), CH-6928 Manno, Switzerland
3
Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, AB T6G 2H1 Edmonton, Canada
4
Department of Mechanical and Aerospace Engineering, Politecnico di Torino, 10129 Torino, Italy
5
Department of Oncology, University of Alberta, AB T6G 1Z2 Edmonton, Canada
*
Author to whom correspondence should be addressed.
Pharmaceuticals 2018, 11(1), 22; https://doi.org/10.3390/ph11010022
Received: 17 January 2018 / Revised: 1 February 2018 / Accepted: 13 February 2018 / Published: 16 February 2018
(This article belongs to the Collection Old Pharmaceuticals with New Applications)
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Abstract

The Toll-Like Receptor 7 (TLR7) is an endosomal membrane receptor involved in the innate immune system response. Its best-known small molecule activators are imidazoquinoline derivatives such as imiquimod (R-837) and resiquimod (R-848). Recently, an interaction between R-837 and the colchicine binding site of tubulin was reported. To investigate the possibility of an interaction between structural analogues of colchicine and the TLR7, a recent computational model for the dimeric form of the TLR7 receptor was used to determine a possible interaction with a colchicine derivative called CR42-24, active as a tubulin polymerization inhibitor. The estimated values of the binding energy of this molecule with respect to the TLR7 receptor were comparable to the energies of known binders as reported in a previous study. The binding to the TLR7 was further assessed by introducing genetic transformations in the TLR7 gene in cancer cell lines and exposing them to the compound. A negative shift of the IC50 value in terms of cell growth was observed in cell lines carrying the mutated TLR7 gene. The reported study suggests a possible interaction between TLR7 and a colchicine derivative, which can be explored for rational design of new drugs acting on this receptor by using a colchicine scaffold for additional modifications. View Full-Text
Keywords: TLR7; colchicine; imiquimod; innate immune system; off-target interaction TLR7; colchicine; imiquimod; innate immune system; off-target interaction
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MDPI and ACS Style

Gentile, F.; Deriu, M.A.; Barakat, K.; Danani, A.; Tuszynski, J. A Novel Interaction Between the TLR7 and a Colchicine Derivative Revealed Through a Computational and Experimental Study. Pharmaceuticals 2018, 11, 22. https://doi.org/10.3390/ph11010022

AMA Style

Gentile F, Deriu MA, Barakat K, Danani A, Tuszynski J. A Novel Interaction Between the TLR7 and a Colchicine Derivative Revealed Through a Computational and Experimental Study. Pharmaceuticals. 2018; 11(1):22. https://doi.org/10.3390/ph11010022

Chicago/Turabian Style

Gentile, Francesco, Marco A. Deriu, Khaled Barakat, Andrea Danani, and Jack Tuszynski. 2018. "A Novel Interaction Between the TLR7 and a Colchicine Derivative Revealed Through a Computational and Experimental Study" Pharmaceuticals 11, no. 1: 22. https://doi.org/10.3390/ph11010022

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