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Discovery of Some Heterocyclic Molecules as Bone Morphogenetic Protein 2 (BMP-2)-Inducible Kinase Inhibitors: Virtual Screening, ADME Properties, and Molecular Docking Simulations
Bone morphogenetic proteins (BMPs) are growth factors that have a vital role in the production of bone, cartilage, ligaments, and tendons. Tumors’ upregulation of bone morphogenetic proteins (BMPs) and their receptors are key features of cancer progression. Regulation of the BMP kinase system is a n...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9457949/ https://www.ncbi.nlm.nih.gov/pubmed/36080338 http://dx.doi.org/10.3390/molecules27175571 |
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author | Belal, Amany Elkady, Hazem Al-Karmalawy, Ahmed A. Amin, Ali H. Ghoneim, Mohammed M. El-Sherbiny, Mohamed Al-Serwi, Rasha Hamed Abdou, Mohamed Attia Ibrahim, Mona H. Mehany, Ahmed B. M. |
author_facet | Belal, Amany Elkady, Hazem Al-Karmalawy, Ahmed A. Amin, Ali H. Ghoneim, Mohammed M. El-Sherbiny, Mohamed Al-Serwi, Rasha Hamed Abdou, Mohamed Attia Ibrahim, Mona H. Mehany, Ahmed B. M. |
author_sort | Belal, Amany |
collection | PubMed |
description | Bone morphogenetic proteins (BMPs) are growth factors that have a vital role in the production of bone, cartilage, ligaments, and tendons. Tumors’ upregulation of bone morphogenetic proteins (BMPs) and their receptors are key features of cancer progression. Regulation of the BMP kinase system is a new promising strategy for the development of anti-cancer drugs. In this work, based on a careful literature study, a library of benzothiophene and benzofuran derivatives was subjected to different computational techniques to study the effect of chemical structure changes on the ability of these two scaffolds to target BMP-2 inducible kinase, and to reach promising candidates with proposed activity against BMP-2 inducible kinase. The results of screening against Lipinski’s and Veber’s Rules produced twenty-one outside eighty-four compounds having drug-like molecular nature. Computational ADMET studies favored ten compounds (11, 26, 27, 29, 30, 31, 34, 35, 65, and 72) with good pharmacokinetic profile. Computational toxicity studies excluded compound 34 to elect nine compounds for molecular docking studies which displayed eight compounds (26, 27, 29, 30, 31, 35, 65, and 72) as promising BMP-2 inducible kinase inhibitors. The nine fascinating compounds will be subjected to extensive screening against serine/threonine kinases to explore their potential against these critical proteins. These promising candidates based on benzothiophene and benzofuran scaffolds deserve further clinical investigation as BMP-2 kinase inhibitors for the treatment of cancer. |
format | Online Article Text |
id | pubmed-9457949 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-94579492022-09-09 Discovery of Some Heterocyclic Molecules as Bone Morphogenetic Protein 2 (BMP-2)-Inducible Kinase Inhibitors: Virtual Screening, ADME Properties, and Molecular Docking Simulations Belal, Amany Elkady, Hazem Al-Karmalawy, Ahmed A. Amin, Ali H. Ghoneim, Mohammed M. El-Sherbiny, Mohamed Al-Serwi, Rasha Hamed Abdou, Mohamed Attia Ibrahim, Mona H. Mehany, Ahmed B. M. Molecules Article Bone morphogenetic proteins (BMPs) are growth factors that have a vital role in the production of bone, cartilage, ligaments, and tendons. Tumors’ upregulation of bone morphogenetic proteins (BMPs) and their receptors are key features of cancer progression. Regulation of the BMP kinase system is a new promising strategy for the development of anti-cancer drugs. In this work, based on a careful literature study, a library of benzothiophene and benzofuran derivatives was subjected to different computational techniques to study the effect of chemical structure changes on the ability of these two scaffolds to target BMP-2 inducible kinase, and to reach promising candidates with proposed activity against BMP-2 inducible kinase. The results of screening against Lipinski’s and Veber’s Rules produced twenty-one outside eighty-four compounds having drug-like molecular nature. Computational ADMET studies favored ten compounds (11, 26, 27, 29, 30, 31, 34, 35, 65, and 72) with good pharmacokinetic profile. Computational toxicity studies excluded compound 34 to elect nine compounds for molecular docking studies which displayed eight compounds (26, 27, 29, 30, 31, 35, 65, and 72) as promising BMP-2 inducible kinase inhibitors. The nine fascinating compounds will be subjected to extensive screening against serine/threonine kinases to explore their potential against these critical proteins. These promising candidates based on benzothiophene and benzofuran scaffolds deserve further clinical investigation as BMP-2 kinase inhibitors for the treatment of cancer. MDPI 2022-08-30 /pmc/articles/PMC9457949/ /pubmed/36080338 http://dx.doi.org/10.3390/molecules27175571 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Belal, Amany Elkady, Hazem Al-Karmalawy, Ahmed A. Amin, Ali H. Ghoneim, Mohammed M. El-Sherbiny, Mohamed Al-Serwi, Rasha Hamed Abdou, Mohamed Attia Ibrahim, Mona H. Mehany, Ahmed B. M. Discovery of Some Heterocyclic Molecules as Bone Morphogenetic Protein 2 (BMP-2)-Inducible Kinase Inhibitors: Virtual Screening, ADME Properties, and Molecular Docking Simulations |
title | Discovery of Some Heterocyclic Molecules as Bone Morphogenetic Protein 2 (BMP-2)-Inducible Kinase Inhibitors: Virtual Screening, ADME Properties, and Molecular Docking Simulations |
title_full | Discovery of Some Heterocyclic Molecules as Bone Morphogenetic Protein 2 (BMP-2)-Inducible Kinase Inhibitors: Virtual Screening, ADME Properties, and Molecular Docking Simulations |
title_fullStr | Discovery of Some Heterocyclic Molecules as Bone Morphogenetic Protein 2 (BMP-2)-Inducible Kinase Inhibitors: Virtual Screening, ADME Properties, and Molecular Docking Simulations |
title_full_unstemmed | Discovery of Some Heterocyclic Molecules as Bone Morphogenetic Protein 2 (BMP-2)-Inducible Kinase Inhibitors: Virtual Screening, ADME Properties, and Molecular Docking Simulations |
title_short | Discovery of Some Heterocyclic Molecules as Bone Morphogenetic Protein 2 (BMP-2)-Inducible Kinase Inhibitors: Virtual Screening, ADME Properties, and Molecular Docking Simulations |
title_sort | discovery of some heterocyclic molecules as bone morphogenetic protein 2 (bmp-2)-inducible kinase inhibitors: virtual screening, adme properties, and molecular docking simulations |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9457949/ https://www.ncbi.nlm.nih.gov/pubmed/36080338 http://dx.doi.org/10.3390/molecules27175571 |
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