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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| Format: | Article |
| Language: | English |
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MDPI AG
2023-02-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/28/5/2058 |
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| author | Violina T. Angelova Teodora Tatarova Rositsa Mihaylova Nikolay Vassilev Boris Petrov Zvetanka Zhivkova Irini Doytchinova |
| author_facet | Violina T. Angelova Teodora Tatarova Rositsa Mihaylova Nikolay Vassilev Boris Petrov Zvetanka Zhivkova Irini Doytchinova |
| author_sort | Violina T. Angelova |
| collection | DOAJ |
| 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 (<b>1a</b>, <b>1b</b>, <b>1c</b>, and <b>1e</b>) show IC<sub>50</sub> values below 1 μM on MCF-7 and one (<b>1e</b>) on MDA-MB-231. The presence of an indole ring bearing 5-Cl, 5-OCH<sub>3</sub>, or 1-COCH<sub>3</sub> has the most pronounced positive effect on the cytotoxic activity of the arylsulfonylhydrazones designed in the present study. |
| first_indexed | 2024-03-11T07:17:53Z |
| format | Article |
| id | doaj.art-ada11a4569994a539f734932b8dee118 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-11T07:17:53Z |
| publishDate | 2023-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-ada11a4569994a539f734932b8dee1182023-11-17T08:11:25ZengMDPI AGMolecules1420-30492023-02-01285205810.3390/molecules28052058Novel Arylsulfonylhydrazones as Breast Anticancer Agents Discovered by Quantitative Structure-Activity RelationshipsViolina T. Angelova0Teodora Tatarova1Rositsa Mihaylova2Nikolay Vassilev3Boris Petrov4Zvetanka Zhivkova5Irini Doytchinova6Faculty of Pharmacy, Medical University of Sofia, 1000 Sofia, BulgariaFaculty of Pharmacy, Medical University of Sofia, 1000 Sofia, BulgariaFaculty of Pharmacy, Medical University of Sofia, 1000 Sofia, BulgariaLaboratory “Nuclear Magnetic Resonance”, Institute of Organic Chemistry with Centre of Phytochemistry, Bulgarian Academy of Sciences, 1113 Sofia, BulgariaFaculty of Pharmacy, Medical University of Sofia, 1000 Sofia, BulgariaFaculty of Pharmacy, Medical University of Sofia, 1000 Sofia, BulgariaFaculty of Pharmacy, Medical University of Sofia, 1000 Sofia, BulgariaBreast 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 (<b>1a</b>, <b>1b</b>, <b>1c</b>, and <b>1e</b>) show IC<sub>50</sub> values below 1 μM on MCF-7 and one (<b>1e</b>) on MDA-MB-231. The presence of an indole ring bearing 5-Cl, 5-OCH<sub>3</sub>, or 1-COCH<sub>3</sub> has the most pronounced positive effect on the cytotoxic activity of the arylsulfonylhydrazones designed in the present study.https://www.mdpi.com/1420-3049/28/5/2058sulfonyl hydrazonesMCF-7MDA-MB-231QSARbreast canceranticancer activity |
| spellingShingle | Violina T. Angelova Teodora Tatarova Rositsa Mihaylova Nikolay Vassilev Boris Petrov Zvetanka Zhivkova Irini Doytchinova Novel Arylsulfonylhydrazones as Breast Anticancer Agents Discovered by Quantitative Structure-Activity Relationships Molecules sulfonyl hydrazones MCF-7 MDA-MB-231 QSAR breast cancer anticancer activity |
| 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 | sulfonyl hydrazones MCF-7 MDA-MB-231 QSAR breast cancer anticancer activity |
| url | https://www.mdpi.com/1420-3049/28/5/2058 |
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