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Structure-Activity Relationship Studies Based on 3D-QSAR CoMFA/CoMSIA for Thieno-Pyrimidine Derivatives as Triple Negative Breast Cancer Inhibitors
Triple-negative breast cancer (TNBC) is defined as a kind of breast cancer that lacks estrogen receptors (ER), progesterone receptors (PR), and human epidermal growth factor receptors (HER2). This cancer accounts for 10–15% of all breast cancers and has the features of high invasiveness and metastat...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9698756/ https://www.ncbi.nlm.nih.gov/pubmed/36432075 http://dx.doi.org/10.3390/molecules27227974 |
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author | Kim, Jin-Hee Jeong, Jin-Hyun |
author_facet | Kim, Jin-Hee Jeong, Jin-Hyun |
author_sort | Kim, Jin-Hee |
collection | PubMed |
description | Triple-negative breast cancer (TNBC) is defined as a kind of breast cancer that lacks estrogen receptors (ER), progesterone receptors (PR), and human epidermal growth factor receptors (HER2). This cancer accounts for 10–15% of all breast cancers and has the features of high invasiveness and metastatic potential. The treatment regimens are still lacking and need to develop novel inhibitors for therapeutic strategies. Three-dimensional quantitative structure-activity relationship (3D-QSAR) analyses, based on a series of forty-seven thieno-pyrimidine derivatives, were performed to identify the key structural features for the inhibitory biological activities. The established comparative molecular field analysis (CoMFA) presented a leave-one-out cross-validated correlation coefficient q(2) of 0.818 and a determination coefficient r(2) of 0.917. In comparative molecular similarity indices analysis (CoMSIA), a q(2) of 0.801 and an r(2) of 0.897 were exhibited. The predictive capability of these models was confirmed by using external validation and was further validated by the progressive scrambling stability test. From these results of validation, the models were determined to be statistically reliable and robust. This study could provide valuable information for further optimization and design of novel inhibitors against metastatic breast cancer. |
format | Online Article Text |
id | pubmed-9698756 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-96987562022-11-26 Structure-Activity Relationship Studies Based on 3D-QSAR CoMFA/CoMSIA for Thieno-Pyrimidine Derivatives as Triple Negative Breast Cancer Inhibitors Kim, Jin-Hee Jeong, Jin-Hyun Molecules Article Triple-negative breast cancer (TNBC) is defined as a kind of breast cancer that lacks estrogen receptors (ER), progesterone receptors (PR), and human epidermal growth factor receptors (HER2). This cancer accounts for 10–15% of all breast cancers and has the features of high invasiveness and metastatic potential. The treatment regimens are still lacking and need to develop novel inhibitors for therapeutic strategies. Three-dimensional quantitative structure-activity relationship (3D-QSAR) analyses, based on a series of forty-seven thieno-pyrimidine derivatives, were performed to identify the key structural features for the inhibitory biological activities. The established comparative molecular field analysis (CoMFA) presented a leave-one-out cross-validated correlation coefficient q(2) of 0.818 and a determination coefficient r(2) of 0.917. In comparative molecular similarity indices analysis (CoMSIA), a q(2) of 0.801 and an r(2) of 0.897 were exhibited. The predictive capability of these models was confirmed by using external validation and was further validated by the progressive scrambling stability test. From these results of validation, the models were determined to be statistically reliable and robust. This study could provide valuable information for further optimization and design of novel inhibitors against metastatic breast cancer. MDPI 2022-11-17 /pmc/articles/PMC9698756/ /pubmed/36432075 http://dx.doi.org/10.3390/molecules27227974 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 Kim, Jin-Hee Jeong, Jin-Hyun Structure-Activity Relationship Studies Based on 3D-QSAR CoMFA/CoMSIA for Thieno-Pyrimidine Derivatives as Triple Negative Breast Cancer Inhibitors |
title | Structure-Activity Relationship Studies Based on 3D-QSAR CoMFA/CoMSIA for Thieno-Pyrimidine Derivatives as Triple Negative Breast Cancer Inhibitors |
title_full | Structure-Activity Relationship Studies Based on 3D-QSAR CoMFA/CoMSIA for Thieno-Pyrimidine Derivatives as Triple Negative Breast Cancer Inhibitors |
title_fullStr | Structure-Activity Relationship Studies Based on 3D-QSAR CoMFA/CoMSIA for Thieno-Pyrimidine Derivatives as Triple Negative Breast Cancer Inhibitors |
title_full_unstemmed | Structure-Activity Relationship Studies Based on 3D-QSAR CoMFA/CoMSIA for Thieno-Pyrimidine Derivatives as Triple Negative Breast Cancer Inhibitors |
title_short | Structure-Activity Relationship Studies Based on 3D-QSAR CoMFA/CoMSIA for Thieno-Pyrimidine Derivatives as Triple Negative Breast Cancer Inhibitors |
title_sort | structure-activity relationship studies based on 3d-qsar comfa/comsia for thieno-pyrimidine derivatives as triple negative breast cancer inhibitors |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9698756/ https://www.ncbi.nlm.nih.gov/pubmed/36432075 http://dx.doi.org/10.3390/molecules27227974 |
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