Synthesis and Antiproliferative Activity of 2,6-Disubstituted Imidazo[4,5-<i>b</i>]pyridines Prepared by Suzuki Cross Coupling
A series of novel 2,6-diphenyl substituted imidazo[4,5-<i>b</i>]pyridines was designed and synthesized using optimized Suzuki cross coupling to evaluate their biological activity <i>in vitro</i>. The conditions of the Suzuki coupling were evaluated and optimized using a model...
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MDPI AG
2023-10-01
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| Online Access: | https://www.mdpi.com/1420-3049/28/20/7208 |
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| author | Ida Boček Pavlinac Mirna Dragić Leentje Persoons Dirk Daelemans Marijana Hranjec |
| author_facet | Ida Boček Pavlinac Mirna Dragić Leentje Persoons Dirk Daelemans Marijana Hranjec |
| author_sort | Ida Boček Pavlinac |
| collection | DOAJ |
| description | A series of novel 2,6-diphenyl substituted imidazo[4,5-<i>b</i>]pyridines was designed and synthesized using optimized Suzuki cross coupling to evaluate their biological activity <i>in vitro</i>. The conditions of the Suzuki coupling were evaluated and optimized using a model reaction. To study the influence of the substituents on the biological activity, we prepared <i>N</i>-unsubstituted and <i>N</i>-methyl substituted imidazo[4,5-<i>b</i>]pyridines with different substituents at the <i>para</i> position on the phenyl ring placed at position 6 on the heterocyclic scaffold. Antiproliferative activity was determined on diverse human cancer cell lines, and the selectivity of compounds with promising antiproliferative activity was determined on normal peripheral blood mononuclear cells (PBMC). Pronounced antiproliferative activity was observed for <i>p</i>-hydroxy substituted derivatives <b>13</b> and <b>19</b>, both displaying strong activity against most of the tested cell lines (IC<sub>50</sub> 1.45–4.25 μM). The unsubstituted <i>N</i>-methyl derivative <b>19</b> proved to be the most active derivative. There was a dose-dependent accumulation of G2/M arrested cells in several cancer cell lines after exposure to compound <b>19</b>, implying a cell cycle-phase-specific mechanism of action. Additionally, the novel series of derivatives was evaluated for antiviral activity against a broad panel of viruses, yet the majority of tested compounds did not show antiviral activity. |
| first_indexed | 2024-03-10T21:00:41Z |
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| id | doaj.art-6ad05f9049354cdebfc26b410827e2aa |
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| last_indexed | 2024-03-10T21:00:41Z |
| publishDate | 2023-10-01 |
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| series | Molecules |
| spelling | doaj.art-6ad05f9049354cdebfc26b410827e2aa2023-11-19T17:34:19ZengMDPI AGMolecules1420-30492023-10-012820720810.3390/molecules28207208Synthesis and Antiproliferative Activity of 2,6-Disubstituted Imidazo[4,5-<i>b</i>]pyridines Prepared by Suzuki Cross CouplingIda Boček Pavlinac0Mirna Dragić1Leentje Persoons2Dirk Daelemans3Marijana Hranjec4Department of Organic Chemistry, Faculty of Chemical Engineering and Technology, University of Zagreb, Marulićev trg 19, HR-10000 Zagreb, CroatiaDepartment of Organic Chemistry, Faculty of Chemical Engineering and Technology, University of Zagreb, Marulićev trg 19, HR-10000 Zagreb, CroatiaKU Leuven Department of Microbiology, Immunology and Transplantation, Laboratory of Virology and Chemotherapy, Rega Institute, 3000 Leuven, BelgiumKU Leuven Department of Microbiology, Immunology and Transplantation, Laboratory of Virology and Chemotherapy, Rega Institute, 3000 Leuven, BelgiumDepartment of Organic Chemistry, Faculty of Chemical Engineering and Technology, University of Zagreb, Marulićev trg 19, HR-10000 Zagreb, CroatiaA series of novel 2,6-diphenyl substituted imidazo[4,5-<i>b</i>]pyridines was designed and synthesized using optimized Suzuki cross coupling to evaluate their biological activity <i>in vitro</i>. The conditions of the Suzuki coupling were evaluated and optimized using a model reaction. To study the influence of the substituents on the biological activity, we prepared <i>N</i>-unsubstituted and <i>N</i>-methyl substituted imidazo[4,5-<i>b</i>]pyridines with different substituents at the <i>para</i> position on the phenyl ring placed at position 6 on the heterocyclic scaffold. Antiproliferative activity was determined on diverse human cancer cell lines, and the selectivity of compounds with promising antiproliferative activity was determined on normal peripheral blood mononuclear cells (PBMC). Pronounced antiproliferative activity was observed for <i>p</i>-hydroxy substituted derivatives <b>13</b> and <b>19</b>, both displaying strong activity against most of the tested cell lines (IC<sub>50</sub> 1.45–4.25 μM). The unsubstituted <i>N</i>-methyl derivative <b>19</b> proved to be the most active derivative. There was a dose-dependent accumulation of G2/M arrested cells in several cancer cell lines after exposure to compound <b>19</b>, implying a cell cycle-phase-specific mechanism of action. Additionally, the novel series of derivatives was evaluated for antiviral activity against a broad panel of viruses, yet the majority of tested compounds did not show antiviral activity.https://www.mdpi.com/1420-3049/28/20/7208antiproliferative activityantiviral activityimidazo[4,5-<i>b</i>]pyridinesSuzuki couplingoptimization |
| spellingShingle | Ida Boček Pavlinac Mirna Dragić Leentje Persoons Dirk Daelemans Marijana Hranjec Synthesis and Antiproliferative Activity of 2,6-Disubstituted Imidazo[4,5-<i>b</i>]pyridines Prepared by Suzuki Cross Coupling Molecules antiproliferative activity antiviral activity imidazo[4,5-<i>b</i>]pyridines Suzuki coupling optimization |
| title | Synthesis and Antiproliferative Activity of 2,6-Disubstituted Imidazo[4,5-<i>b</i>]pyridines Prepared by Suzuki Cross Coupling |
| title_full | Synthesis and Antiproliferative Activity of 2,6-Disubstituted Imidazo[4,5-<i>b</i>]pyridines Prepared by Suzuki Cross Coupling |
| title_fullStr | Synthesis and Antiproliferative Activity of 2,6-Disubstituted Imidazo[4,5-<i>b</i>]pyridines Prepared by Suzuki Cross Coupling |
| title_full_unstemmed | Synthesis and Antiproliferative Activity of 2,6-Disubstituted Imidazo[4,5-<i>b</i>]pyridines Prepared by Suzuki Cross Coupling |
| title_short | Synthesis and Antiproliferative Activity of 2,6-Disubstituted Imidazo[4,5-<i>b</i>]pyridines Prepared by Suzuki Cross Coupling |
| title_sort | synthesis and antiproliferative activity of 2 6 disubstituted imidazo 4 5 i b i pyridines prepared by suzuki cross coupling |
| topic | antiproliferative activity antiviral activity imidazo[4,5-<i>b</i>]pyridines Suzuki coupling optimization |
| url | https://www.mdpi.com/1420-3049/28/20/7208 |
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