Identification of non-classical hCA XII inhibitors using combination of computational approaches for drug design and discovery

Abstract Human carbonic anhydrase XII (hCA XII) isozyme is of high therapeutic value as a pharmacological target and biomarker for different types of cancer. The hCA XII is one of the crucial effectors that regulates extracellular and intracellular pH and affects cancer cell proliferation, invasion,...

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Autores principales:	Mohammad M. Al-Sanea, Garri Chilingaryan, Narek Abelyan, Grigor Arakelov, Harutyun Sahakyan, Vahram G. Arakelov, Karen Nazaryan, Shaimaa Hussein, Gharam M. Alazmi, Haifa E. Alsharari, Waad M. Al-faraj, Faten S. Alruwaili, Nouf Q. Albilasi, Tahani S. Alsharari, Abdulaziz A. S. Alsaleh, Turki M. Alazmi, Atiah H. Almalki, Nasser H. Alotaibi, Mohamed A. Abdelgawad
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/2c1d4ac6a4d343049a08b2c705fe9f50
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spelling	oai:doaj.org-article:2c1d4ac6a4d343049a08b2c705fe9f502021-12-02T16:06:41ZIdentification of non-classical hCA XII inhibitors using combination of computational approaches for drug design and discovery10.1038/s41598-021-94809-x2045-2322https://doaj.org/article/2c1d4ac6a4d343049a08b2c705fe9f502021-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-94809-xhttps://doaj.org/toc/2045-2322Abstract Human carbonic anhydrase XII (hCA XII) isozyme is of high therapeutic value as a pharmacological target and biomarker for different types of cancer. The hCA XII is one of the crucial effectors that regulates extracellular and intracellular pH and affects cancer cell proliferation, invasion, growth and metastasis. Despite the fact that interaction features of hCAs inhibitors with the catalytic site of the enzyme are well described, lack in the selectivity of the traditional hCA inhibitors based on the sulfonamide group or related motifs is an urgent issue. Moreover, drugs containing sulfanomides can cause sulfa allergies. Thus, identification of novel non-classical inhibitors of hCA XII is of high priority and is currently the subject of a vast field of study. This study was devoted to the identification of novel potential hCA XII inhibitors using comprehensive set of computational approaches for drug design discovery: generation and validation of structure- and ligand-based pharmacophore models, molecular docking, re-scoring of virtual screening results with MMGBSA, molecular dynamics simulations, etc. As the results of the study several compounds with alternative to classical inhibitors chemical scaffolds, in particular one of coumarins derivative, have been identified and are of high interest as potential non-classical hCA XII inhibitors.Mohammad M. Al-SaneaGarri ChilingaryanNarek AbelyanGrigor ArakelovHarutyun SahakyanVahram G. ArakelovKaren NazaryanShaimaa HusseinGharam M. AlazmiHaifa E. AlsharariWaad M. Al-farajFaten S. AlruwailiNouf Q. AlbilasiTahani S. AlsharariAbdulaziz A. S. AlsalehTurki M. AlazmiAtiah H. AlmalkiNasser H. AlotaibiMohamed A. AbdelgawadNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Mohammad M. Al-Sanea Garri Chilingaryan Narek Abelyan Grigor Arakelov Harutyun Sahakyan Vahram G. Arakelov Karen Nazaryan Shaimaa Hussein Gharam M. Alazmi Haifa E. Alsharari Waad M. Al-faraj Faten S. Alruwaili Nouf Q. Albilasi Tahani S. Alsharari Abdulaziz A. S. Alsaleh Turki M. Alazmi Atiah H. Almalki Nasser H. Alotaibi Mohamed A. Abdelgawad Identification of non-classical hCA XII inhibitors using combination of computational approaches for drug design and discovery
description	Abstract Human carbonic anhydrase XII (hCA XII) isozyme is of high therapeutic value as a pharmacological target and biomarker for different types of cancer. The hCA XII is one of the crucial effectors that regulates extracellular and intracellular pH and affects cancer cell proliferation, invasion, growth and metastasis. Despite the fact that interaction features of hCAs inhibitors with the catalytic site of the enzyme are well described, lack in the selectivity of the traditional hCA inhibitors based on the sulfonamide group or related motifs is an urgent issue. Moreover, drugs containing sulfanomides can cause sulfa allergies. Thus, identification of novel non-classical inhibitors of hCA XII is of high priority and is currently the subject of a vast field of study. This study was devoted to the identification of novel potential hCA XII inhibitors using comprehensive set of computational approaches for drug design discovery: generation and validation of structure- and ligand-based pharmacophore models, molecular docking, re-scoring of virtual screening results with MMGBSA, molecular dynamics simulations, etc. As the results of the study several compounds with alternative to classical inhibitors chemical scaffolds, in particular one of coumarins derivative, have been identified and are of high interest as potential non-classical hCA XII inhibitors.
format	article
author	Mohammad M. Al-Sanea Garri Chilingaryan Narek Abelyan Grigor Arakelov Harutyun Sahakyan Vahram G. Arakelov Karen Nazaryan Shaimaa Hussein Gharam M. Alazmi Haifa E. Alsharari Waad M. Al-faraj Faten S. Alruwaili Nouf Q. Albilasi Tahani S. Alsharari Abdulaziz A. S. Alsaleh Turki M. Alazmi Atiah H. Almalki Nasser H. Alotaibi Mohamed A. Abdelgawad
author_facet	Mohammad M. Al-Sanea Garri Chilingaryan Narek Abelyan Grigor Arakelov Harutyun Sahakyan Vahram G. Arakelov Karen Nazaryan Shaimaa Hussein Gharam M. Alazmi Haifa E. Alsharari Waad M. Al-faraj Faten S. Alruwaili Nouf Q. Albilasi Tahani S. Alsharari Abdulaziz A. S. Alsaleh Turki M. Alazmi Atiah H. Almalki Nasser H. Alotaibi Mohamed A. Abdelgawad
author_sort	Mohammad M. Al-Sanea
title	Identification of non-classical hCA XII inhibitors using combination of computational approaches for drug design and discovery
title_short	Identification of non-classical hCA XII inhibitors using combination of computational approaches for drug design and discovery
title_full	Identification of non-classical hCA XII inhibitors using combination of computational approaches for drug design and discovery
title_fullStr	Identification of non-classical hCA XII inhibitors using combination of computational approaches for drug design and discovery
title_full_unstemmed	Identification of non-classical hCA XII inhibitors using combination of computational approaches for drug design and discovery
title_sort	identification of non-classical hca xii inhibitors using combination of computational approaches for drug design and discovery
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/2c1d4ac6a4d343049a08b2c705fe9f50
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Identification of non-classical hCA XII inhibitors using combination of computational approaches for drug design and discovery

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