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Novel Arylsulfonylhydrazones as Breast Anticancer Agents Discovered by Quantitative Structure-Activity Relationships

Breast cancer (BC) is the second leading cause of cancer death in women, with more than 600,000 deaths annually. Despite the progress that has been made in early diagnosis and treatment of this disease, there is still a significant need for more effective drugs with fewer side effects. In the presen...

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Autores principales: Angelova, Violina T., Tatarova, Teodora, Mihaylova, Rositsa, Vassilev, Nikolay, Petrov, Boris, Zhivkova, Zvetanka, Doytchinova, Irini
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10004090/
https://www.ncbi.nlm.nih.gov/pubmed/36903304
http://dx.doi.org/10.3390/molecules28052058
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author Angelova, Violina T.
Tatarova, Teodora
Mihaylova, Rositsa
Vassilev, Nikolay
Petrov, Boris
Zhivkova, Zvetanka
Doytchinova, Irini
author_facet Angelova, Violina T.
Tatarova, Teodora
Mihaylova, Rositsa
Vassilev, Nikolay
Petrov, Boris
Zhivkova, Zvetanka
Doytchinova, Irini
author_sort Angelova, Violina T.
collection PubMed
description Breast cancer (BC) is the second leading cause of cancer death in women, with more than 600,000 deaths annually. Despite the progress that has been made in early diagnosis and treatment of this disease, there is still a significant need for more effective drugs with fewer side effects. In the present study, we derive QSAR models with good predictive ability based on data from the literature and reveal the relationships between the chemical structures of a set of arylsulfonylhydrazones and their anticancer activity on human ER+ breast adenocarcinoma and triple-negative breast (TNBC) adenocarcinoma. Applying the derived knowledge, we design nine novel arylsulfonylhydrazones and screen them in silico for drug likeness. All nine molecules show suitable drug and lead properties. They are synthesized and tested in vitro for anticancer activity on MCF-7 and MDA-MB-231 cell lines. Most of the compounds are more active than predicted and show stronger activity on MCF-7 than on MDA-MB-231. Four of the compounds (1a, 1b, 1c, and 1e) show IC(50) values below 1 μM on MCF-7 and one (1e) on MDA-MB-231. The presence of an indole ring bearing 5-Cl, 5-OCH(3), or 1-COCH(3) has the most pronounced positive effect on the cytotoxic activity of the arylsulfonylhydrazones designed in the present study.
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spelling pubmed-100040902023-03-11 Novel Arylsulfonylhydrazones as Breast Anticancer Agents Discovered by Quantitative Structure-Activity Relationships Angelova, Violina T. Tatarova, Teodora Mihaylova, Rositsa Vassilev, Nikolay Petrov, Boris Zhivkova, Zvetanka Doytchinova, Irini Molecules Article Breast cancer (BC) is the second leading cause of cancer death in women, with more than 600,000 deaths annually. Despite the progress that has been made in early diagnosis and treatment of this disease, there is still a significant need for more effective drugs with fewer side effects. In the present study, we derive QSAR models with good predictive ability based on data from the literature and reveal the relationships between the chemical structures of a set of arylsulfonylhydrazones and their anticancer activity on human ER+ breast adenocarcinoma and triple-negative breast (TNBC) adenocarcinoma. Applying the derived knowledge, we design nine novel arylsulfonylhydrazones and screen them in silico for drug likeness. All nine molecules show suitable drug and lead properties. They are synthesized and tested in vitro for anticancer activity on MCF-7 and MDA-MB-231 cell lines. Most of the compounds are more active than predicted and show stronger activity on MCF-7 than on MDA-MB-231. Four of the compounds (1a, 1b, 1c, and 1e) show IC(50) values below 1 μM on MCF-7 and one (1e) on MDA-MB-231. The presence of an indole ring bearing 5-Cl, 5-OCH(3), or 1-COCH(3) has the most pronounced positive effect on the cytotoxic activity of the arylsulfonylhydrazones designed in the present study. MDPI 2023-02-22 /pmc/articles/PMC10004090/ /pubmed/36903304 http://dx.doi.org/10.3390/molecules28052058 Text en © 2023 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
Angelova, Violina T.
Tatarova, Teodora
Mihaylova, Rositsa
Vassilev, Nikolay
Petrov, Boris
Zhivkova, Zvetanka
Doytchinova, Irini
Novel Arylsulfonylhydrazones as Breast Anticancer Agents Discovered by Quantitative Structure-Activity Relationships
title Novel Arylsulfonylhydrazones as Breast Anticancer Agents Discovered by Quantitative Structure-Activity Relationships
title_full Novel Arylsulfonylhydrazones as Breast Anticancer Agents Discovered by Quantitative Structure-Activity Relationships
title_fullStr Novel Arylsulfonylhydrazones as Breast Anticancer Agents Discovered by Quantitative Structure-Activity Relationships
title_full_unstemmed Novel Arylsulfonylhydrazones as Breast Anticancer Agents Discovered by Quantitative Structure-Activity Relationships
title_short Novel Arylsulfonylhydrazones as Breast Anticancer Agents Discovered by Quantitative Structure-Activity Relationships
title_sort novel arylsulfonylhydrazones as breast anticancer agents discovered by quantitative structure-activity relationships
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10004090/
https://www.ncbi.nlm.nih.gov/pubmed/36903304
http://dx.doi.org/10.3390/molecules28052058
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