Systematic Studies on Anti-Cancer Evaluation of Stilbene and Dibenzo[<i>b,f</i>]oxepine Derivatives
Cancer is one of the most common causes of human death worldwide; thus, numerous therapies, including chemotherapy, have been and are being continuously developed. In cancer cells, an aberrant mitotic spindle—a microtubule-based structure necessary for the equal splitting of genetic material between...
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MDPI AG
2023-04-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/28/8/3558 |
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| author | Filip Borys Piotr Tobiasz Marcin Poterała Hanna Fabczak Hanna Krawczyk Ewa Joachimiak |
| author_facet | Filip Borys Piotr Tobiasz Marcin Poterała Hanna Fabczak Hanna Krawczyk Ewa Joachimiak |
| author_sort | Filip Borys |
| collection | DOAJ |
| description | Cancer is one of the most common causes of human death worldwide; thus, numerous therapies, including chemotherapy, have been and are being continuously developed. In cancer cells, an aberrant mitotic spindle—a microtubule-based structure necessary for the equal splitting of genetic material between daughter cells—leads to genetic instability, one of the hallmarks of cancer. Thus, the building block of microtubules, tubulin, which is a heterodimer formed from α- and β-tubulin proteins, is a useful target in anti-cancer research. The surface of tubulin forms several pockets, i.e., sites that can bind factors that affect microtubules’ stability. Colchicine pockets accommodate agents that induce microtubule depolymerization and, in contrast to factors that bind to other tubulin pockets, overcome multi-drug resistance. Therefore, colchicine-pocket-binding agents are of interest as anti-cancer drugs. Among the various colchicine-site-binding compounds, stilbenoids and their derivatives have been extensively studied. Herein, we report systematic studies on the antiproliferative activity of selected stilbenes and oxepine derivatives against two cancer cell lines—HCT116 and MCF-7—and two normal cell lines—HEK293 and HDF-A. The results of molecular modeling, antiproliferative activity, and immunofluorescence analyses revealed that compounds <b>1a</b>, <b>1c</b>, <b>1d</b>, <b>1i</b>, <b>2i</b>, <b>2j</b>, and <b>3h</b> were the most cytotoxic and acted by interacting with tubulin heterodimers, leading to the disruption of the microtubular cytoskeleton. |
| first_indexed | 2024-03-11T04:41:52Z |
| format | Article |
| id | doaj.art-bbe36f7a633d428bb344c4e372463727 |
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| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-11T04:41:52Z |
| publishDate | 2023-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-bbe36f7a633d428bb344c4e3724637272023-11-17T20:40:43ZengMDPI AGMolecules1420-30492023-04-01288355810.3390/molecules28083558Systematic Studies on Anti-Cancer Evaluation of Stilbene and Dibenzo[<i>b,f</i>]oxepine DerivativesFilip Borys0Piotr Tobiasz1Marcin Poterała2Hanna Fabczak3Hanna Krawczyk4Ewa Joachimiak5Department of Organic Chemistry, Faculty of Chemistry, Warsaw University of Technology, 00-664 Warsaw, PolandDepartment of Organic Chemistry, Faculty of Chemistry, Warsaw University of Technology, 00-664 Warsaw, PolandDepartment of Organic Chemistry, Faculty of Chemistry, Warsaw University of Technology, 00-664 Warsaw, PolandNencki Institute of Experimental Biology, Polish Academy of Sciences, 02-093 Warsaw, PolandDepartment of Organic Chemistry, Faculty of Chemistry, Warsaw University of Technology, 00-664 Warsaw, PolandNencki Institute of Experimental Biology, Polish Academy of Sciences, 02-093 Warsaw, PolandCancer is one of the most common causes of human death worldwide; thus, numerous therapies, including chemotherapy, have been and are being continuously developed. In cancer cells, an aberrant mitotic spindle—a microtubule-based structure necessary for the equal splitting of genetic material between daughter cells—leads to genetic instability, one of the hallmarks of cancer. Thus, the building block of microtubules, tubulin, which is a heterodimer formed from α- and β-tubulin proteins, is a useful target in anti-cancer research. The surface of tubulin forms several pockets, i.e., sites that can bind factors that affect microtubules’ stability. Colchicine pockets accommodate agents that induce microtubule depolymerization and, in contrast to factors that bind to other tubulin pockets, overcome multi-drug resistance. Therefore, colchicine-pocket-binding agents are of interest as anti-cancer drugs. Among the various colchicine-site-binding compounds, stilbenoids and their derivatives have been extensively studied. Herein, we report systematic studies on the antiproliferative activity of selected stilbenes and oxepine derivatives against two cancer cell lines—HCT116 and MCF-7—and two normal cell lines—HEK293 and HDF-A. The results of molecular modeling, antiproliferative activity, and immunofluorescence analyses revealed that compounds <b>1a</b>, <b>1c</b>, <b>1d</b>, <b>1i</b>, <b>2i</b>, <b>2j</b>, and <b>3h</b> were the most cytotoxic and acted by interacting with tubulin heterodimers, leading to the disruption of the microtubular cytoskeleton.https://www.mdpi.com/1420-3049/28/8/3558dibenzo[<i>b,f</i>]oxepinebiological activitycancer cellmicrotubuletubulincolchicine-binding site |
| spellingShingle | Filip Borys Piotr Tobiasz Marcin Poterała Hanna Fabczak Hanna Krawczyk Ewa Joachimiak Systematic Studies on Anti-Cancer Evaluation of Stilbene and Dibenzo[<i>b,f</i>]oxepine Derivatives Molecules dibenzo[<i>b,f</i>]oxepine biological activity cancer cell microtubule tubulin colchicine-binding site |
| title | Systematic Studies on Anti-Cancer Evaluation of Stilbene and Dibenzo[<i>b,f</i>]oxepine Derivatives |
| title_full | Systematic Studies on Anti-Cancer Evaluation of Stilbene and Dibenzo[<i>b,f</i>]oxepine Derivatives |
| title_fullStr | Systematic Studies on Anti-Cancer Evaluation of Stilbene and Dibenzo[<i>b,f</i>]oxepine Derivatives |
| title_full_unstemmed | Systematic Studies on Anti-Cancer Evaluation of Stilbene and Dibenzo[<i>b,f</i>]oxepine Derivatives |
| title_short | Systematic Studies on Anti-Cancer Evaluation of Stilbene and Dibenzo[<i>b,f</i>]oxepine Derivatives |
| title_sort | systematic studies on anti cancer evaluation of stilbene and dibenzo i b f i oxepine derivatives |
| topic | dibenzo[<i>b,f</i>]oxepine biological activity cancer cell microtubule tubulin colchicine-binding site |
| url | https://www.mdpi.com/1420-3049/28/8/3558 |
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