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In-silico Investigation of Tubulin Binding Modes of a Series of Novel Antiproliferative Spiroisoxazoline Compounds Using Docking Studies

Interference with microtubule polymerization results in cell cycle arrest leading to cell death. Colchicine is a well-known microtubule polymerization inhibitor which does so by binding to a specific site on tubulin. A set of 3', 4'-bis (substituted phenyl)-4'H-spiro [indene-2, 5'...

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Autores principales: Abolhasani, Hoda, Zarghi, Afshin, Hamzeh-Mivehroud, Maryam, Alizadeh, Ali Akbar, Shahbazi Mojarrad, Javid, Dastmalchi, Siavoush
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Shaheed Beheshti University of Medical Sciences 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4277627/
https://www.ncbi.nlm.nih.gov/pubmed/25561920
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author Abolhasani, Hoda
Zarghi, Afshin
Hamzeh-Mivehroud, Maryam
Alizadeh, Ali Akbar
Shahbazi Mojarrad, Javid
Dastmalchi, Siavoush
author_facet Abolhasani, Hoda
Zarghi, Afshin
Hamzeh-Mivehroud, Maryam
Alizadeh, Ali Akbar
Shahbazi Mojarrad, Javid
Dastmalchi, Siavoush
author_sort Abolhasani, Hoda
collection PubMed
description Interference with microtubule polymerization results in cell cycle arrest leading to cell death. Colchicine is a well-known microtubule polymerization inhibitor which does so by binding to a specific site on tubulin. A set of 3', 4'-bis (substituted phenyl)-4'H-spiro [indene-2, 5'-isoxazol]-1(3H)-one derivatives with known antiproliferative activities were evaluated for their tubulin binding modes. 3D structures of the derivatives were docked into the colchicine binding site of tubulin using GOLD 5.0 program under flexible ligand and semi-flexible receptor condition. The spiroisoxazoline derivatives bind tubulin in a similar manner to colchicine by establishing at least a hydrogen bonding to Cys(241 )as well as hydrophobic interactions with Leu(255), Ile(378) and Lys(254) and few other residues at the binding pocket. It can be concluded that the spiroisoxazoline core structure common to the studied derivatives is a suitable scaffold for placing the antitubulin pharmacophoric groups in appropriate spatial positions required for tubulin binding activity.
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spelling pubmed-42776272015-01-05 In-silico Investigation of Tubulin Binding Modes of a Series of Novel Antiproliferative Spiroisoxazoline Compounds Using Docking Studies Abolhasani, Hoda Zarghi, Afshin Hamzeh-Mivehroud, Maryam Alizadeh, Ali Akbar Shahbazi Mojarrad, Javid Dastmalchi, Siavoush Iran J Pharm Res Original Article Interference with microtubule polymerization results in cell cycle arrest leading to cell death. Colchicine is a well-known microtubule polymerization inhibitor which does so by binding to a specific site on tubulin. A set of 3', 4'-bis (substituted phenyl)-4'H-spiro [indene-2, 5'-isoxazol]-1(3H)-one derivatives with known antiproliferative activities were evaluated for their tubulin binding modes. 3D structures of the derivatives were docked into the colchicine binding site of tubulin using GOLD 5.0 program under flexible ligand and semi-flexible receptor condition. The spiroisoxazoline derivatives bind tubulin in a similar manner to colchicine by establishing at least a hydrogen bonding to Cys(241 )as well as hydrophobic interactions with Leu(255), Ile(378) and Lys(254) and few other residues at the binding pocket. It can be concluded that the spiroisoxazoline core structure common to the studied derivatives is a suitable scaffold for placing the antitubulin pharmacophoric groups in appropriate spatial positions required for tubulin binding activity. Shaheed Beheshti University of Medical Sciences 2015 /pmc/articles/PMC4277627/ /pubmed/25561920 Text en © 2015 by School of Pharmacy, Shaheed Beheshti University of Medical Sciences and Health Services This is an Open Access article distributed under the terms of the Creative Commons Attribution License, (http://creativecommons.org/licenses/by/3.0/) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Article
Abolhasani, Hoda
Zarghi, Afshin
Hamzeh-Mivehroud, Maryam
Alizadeh, Ali Akbar
Shahbazi Mojarrad, Javid
Dastmalchi, Siavoush
In-silico Investigation of Tubulin Binding Modes of a Series of Novel Antiproliferative Spiroisoxazoline Compounds Using Docking Studies
title In-silico Investigation of Tubulin Binding Modes of a Series of Novel Antiproliferative Spiroisoxazoline Compounds Using Docking Studies
title_full In-silico Investigation of Tubulin Binding Modes of a Series of Novel Antiproliferative Spiroisoxazoline Compounds Using Docking Studies
title_fullStr In-silico Investigation of Tubulin Binding Modes of a Series of Novel Antiproliferative Spiroisoxazoline Compounds Using Docking Studies
title_full_unstemmed In-silico Investigation of Tubulin Binding Modes of a Series of Novel Antiproliferative Spiroisoxazoline Compounds Using Docking Studies
title_short In-silico Investigation of Tubulin Binding Modes of a Series of Novel Antiproliferative Spiroisoxazoline Compounds Using Docking Studies
title_sort in-silico investigation of tubulin binding modes of a series of novel antiproliferative spiroisoxazoline compounds using docking studies
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4277627/
https://www.ncbi.nlm.nih.gov/pubmed/25561920
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