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QSAR and Molecular Docking Studies of Pyrimidine-Coumarin-Triazole Conjugates as Prospective Anti-Breast Cancer Agents

Cancer is a life-threatening disease and is the second leading cause of death worldwide. Although many drugs are available for the treatment of cancer, survival outcomes are very low. Hence, rapid development of newer anticancer agents is a prime focus of the medicinal chemistry community. Since the...

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Autores principales: Subramani, Arun Kumar, Sivaperuman, Amuthalakshmi, Natarajan, Ramalakshmi, Bhandare, Richie R., Shaik, Afzal B.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8955476/
https://www.ncbi.nlm.nih.gov/pubmed/35335208
http://dx.doi.org/10.3390/molecules27061845
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author Subramani, Arun Kumar
Sivaperuman, Amuthalakshmi
Natarajan, Ramalakshmi
Bhandare, Richie R.
Shaik, Afzal B.
author_facet Subramani, Arun Kumar
Sivaperuman, Amuthalakshmi
Natarajan, Ramalakshmi
Bhandare, Richie R.
Shaik, Afzal B.
author_sort Subramani, Arun Kumar
collection PubMed
description Cancer is a life-threatening disease and is the second leading cause of death worldwide. Although many drugs are available for the treatment of cancer, survival outcomes are very low. Hence, rapid development of newer anticancer agents is a prime focus of the medicinal chemistry community. Since the recent past, computational methods have been extensively employed for accelerating the drug discovery process. In view of this, in the present study we performed 2D-QSAR (Quantitative Structure-Activity Relationship) analysis of a series of compounds reported with potential anticancer activity against breast cancer cell line MCF7 using QSARINS software. The best four models exhibited a r(2) value of 0.99. From the generated QSAR equations, a series of pyrimidine-coumarin-triazole conjugates were designed and their MCF7 cell inhibitory activities were predicted using the QSAR equations. Furthermore, molecular docking studies were carried out for the designed compounds using AutoDock Vina against dihydrofolate reductase (DHFR), colchicine and vinblastine binding sites of tubulin, the key enzyme targets in breast cancer. The most active compounds identified through these computational studies will be useful for synthesizing and testing them as prospective novel anti-breast cancer agents.
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spelling pubmed-89554762022-03-26 QSAR and Molecular Docking Studies of Pyrimidine-Coumarin-Triazole Conjugates as Prospective Anti-Breast Cancer Agents Subramani, Arun Kumar Sivaperuman, Amuthalakshmi Natarajan, Ramalakshmi Bhandare, Richie R. Shaik, Afzal B. Molecules Article Cancer is a life-threatening disease and is the second leading cause of death worldwide. Although many drugs are available for the treatment of cancer, survival outcomes are very low. Hence, rapid development of newer anticancer agents is a prime focus of the medicinal chemistry community. Since the recent past, computational methods have been extensively employed for accelerating the drug discovery process. In view of this, in the present study we performed 2D-QSAR (Quantitative Structure-Activity Relationship) analysis of a series of compounds reported with potential anticancer activity against breast cancer cell line MCF7 using QSARINS software. The best four models exhibited a r(2) value of 0.99. From the generated QSAR equations, a series of pyrimidine-coumarin-triazole conjugates were designed and their MCF7 cell inhibitory activities were predicted using the QSAR equations. Furthermore, molecular docking studies were carried out for the designed compounds using AutoDock Vina against dihydrofolate reductase (DHFR), colchicine and vinblastine binding sites of tubulin, the key enzyme targets in breast cancer. The most active compounds identified through these computational studies will be useful for synthesizing and testing them as prospective novel anti-breast cancer agents. MDPI 2022-03-11 /pmc/articles/PMC8955476/ /pubmed/35335208 http://dx.doi.org/10.3390/molecules27061845 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
Subramani, Arun Kumar
Sivaperuman, Amuthalakshmi
Natarajan, Ramalakshmi
Bhandare, Richie R.
Shaik, Afzal B.
QSAR and Molecular Docking Studies of Pyrimidine-Coumarin-Triazole Conjugates as Prospective Anti-Breast Cancer Agents
title QSAR and Molecular Docking Studies of Pyrimidine-Coumarin-Triazole Conjugates as Prospective Anti-Breast Cancer Agents
title_full QSAR and Molecular Docking Studies of Pyrimidine-Coumarin-Triazole Conjugates as Prospective Anti-Breast Cancer Agents
title_fullStr QSAR and Molecular Docking Studies of Pyrimidine-Coumarin-Triazole Conjugates as Prospective Anti-Breast Cancer Agents
title_full_unstemmed QSAR and Molecular Docking Studies of Pyrimidine-Coumarin-Triazole Conjugates as Prospective Anti-Breast Cancer Agents
title_short QSAR and Molecular Docking Studies of Pyrimidine-Coumarin-Triazole Conjugates as Prospective Anti-Breast Cancer Agents
title_sort qsar and molecular docking studies of pyrimidine-coumarin-triazole conjugates as prospective anti-breast cancer agents
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8955476/
https://www.ncbi.nlm.nih.gov/pubmed/35335208
http://dx.doi.org/10.3390/molecules27061845
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