Synthesis and Anti-Cancer Activity In Vitro of Synephrine Derivatives
Glucocorticoids (GCs) are routinely used to treat hematological malignancies; however, long-term treatment with GCs can lead to atrophic and metabolic adverse effects. Selective glucocorticoid receptor agonists (SEGRAs) with reduced side effects may act as a superior alternative to GCs. More than 30...
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2024-12-01
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| author | Ekaterina M. Zhidkova Evgeniya S. Oleynik Ekaterina A. Mikhina Daria V. Stepanycheva Diana D. Grigoreva Lyubov E. Grebenkina Kirill V. Gordeev Ekaterina D. Savina Andrey V. Matveev Marianna G. Yakubovskaya Ekaterina A. Lesovaya |
| author_facet | Ekaterina M. Zhidkova Evgeniya S. Oleynik Ekaterina A. Mikhina Daria V. Stepanycheva Diana D. Grigoreva Lyubov E. Grebenkina Kirill V. Gordeev Ekaterina D. Savina Andrey V. Matveev Marianna G. Yakubovskaya Ekaterina A. Lesovaya |
| author_sort | Ekaterina M. Zhidkova |
| collection | DOAJ |
| description | Glucocorticoids (GCs) are routinely used to treat hematological malignancies; however, long-term treatment with GCs can lead to atrophic and metabolic adverse effects. Selective glucocorticoid receptor agonists (SEGRAs) with reduced side effects may act as a superior alternative to GCs. More than 30 SEGRAs have been described so far, yet none of them reached clinical trials for anti-cancer treatment. In the present work, we propose a novel approach to increase the number of potential SEGRAs by obtaining derivatives of synephrine, a molecule of natural origin. We synthesized 26 novel compounds from the class of synephrine derivatives and characterized them by HRMS, and <sup>1</sup>H and <sup>13</sup>C NMR. We evaluated <i>in vitro</i> anti-cancer effects in leukemia K562 and lymphoma Granta cells using the MTT assay and studied their potential affinity for the glucocorticoid receptor (GR) <i>in silico</i> using the molecular docking approach. The novel derivative 1-[4-(benzyloxy)phenyl]-2-(hexylamino)ethanol (<b>10S-E2</b>) with the highest GR affinity <i>in silico</i> exhibited cytotoxic activity against K562 and Granta cells after 24 h of treatment at the concentration of approximately 13 µM which correlated with its highest MolDock Score. The other compound with high GR affinity, 2-(hexylamino)-1-(4-nitrophenyl)ethanol (<b>13S-G2</b>), demonstrated cytotoxicity in both cell lines at concentrations of 50–70 µM. Overall, our results may provide a solid rationale for developing and further investigating synephrine derivatives as SEGRAs with anti-cancer activity. |
| format | Article |
| id | doaj-art-afe55d0166ed4260afa692830aed7644 |
| institution | Kabale University |
| issn | 2218-273X |
| language | English |
| publishDate | 2024-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj-art-afe55d0166ed4260afa692830aed76442025-01-24T13:24:48ZengMDPI AGBiomolecules2218-273X2024-12-01151210.3390/biom15010002Synthesis and Anti-Cancer Activity In Vitro of Synephrine DerivativesEkaterina M. Zhidkova0Evgeniya S. Oleynik1Ekaterina A. Mikhina2Daria V. Stepanycheva3Diana D. Grigoreva4Lyubov E. Grebenkina5Kirill V. Gordeev6Ekaterina D. Savina7Andrey V. Matveev8Marianna G. Yakubovskaya9Ekaterina A. Lesovaya10Department of Chemical Carcinogenesis, Institute of Carcinogenesis, N.N. Blokhin National Medical Research Center for Oncology, Kashirskoe Shosse 24-15, Moscow 115478, RussiaDepartment of Biotechnology and Industrial Pharmacy, Lomonosov Institute of Fine Chemical Technologies, MIREA—Russian Technological University, 86 Vernadsky Prospekt, Moscow 119571, RussiaDepartment of Biotechnology and Industrial Pharmacy, Lomonosov Institute of Fine Chemical Technologies, MIREA—Russian Technological University, 86 Vernadsky Prospekt, Moscow 119571, RussiaDepartment of Chemical Carcinogenesis, Institute of Carcinogenesis, N.N. Blokhin National Medical Research Center for Oncology, Kashirskoe Shosse 24-15, Moscow 115478, RussiaDepartment of Chemical Carcinogenesis, Institute of Carcinogenesis, N.N. Blokhin National Medical Research Center for Oncology, Kashirskoe Shosse 24-15, Moscow 115478, RussiaDepartment of Biotechnology and Industrial Pharmacy, Lomonosov Institute of Fine Chemical Technologies, MIREA—Russian Technological University, 86 Vernadsky Prospekt, Moscow 119571, RussiaFaculty of Pharmacy, Kuban State Medical University, Ministry of Health of Russia, 4 Mitrofan Sedin Str., Krasnodar 350063, RussiaDepartment of Biotechnology and Industrial Pharmacy, Lomonosov Institute of Fine Chemical Technologies, MIREA—Russian Technological University, 86 Vernadsky Prospekt, Moscow 119571, RussiaDepartment of Biotechnology and Industrial Pharmacy, Lomonosov Institute of Fine Chemical Technologies, MIREA—Russian Technological University, 86 Vernadsky Prospekt, Moscow 119571, RussiaDepartment of Chemical Carcinogenesis, Institute of Carcinogenesis, N.N. Blokhin National Medical Research Center for Oncology, Kashirskoe Shosse 24-15, Moscow 115478, RussiaDepartment of Chemical Carcinogenesis, Institute of Carcinogenesis, N.N. Blokhin National Medical Research Center for Oncology, Kashirskoe Shosse 24-15, Moscow 115478, RussiaGlucocorticoids (GCs) are routinely used to treat hematological malignancies; however, long-term treatment with GCs can lead to atrophic and metabolic adverse effects. Selective glucocorticoid receptor agonists (SEGRAs) with reduced side effects may act as a superior alternative to GCs. More than 30 SEGRAs have been described so far, yet none of them reached clinical trials for anti-cancer treatment. In the present work, we propose a novel approach to increase the number of potential SEGRAs by obtaining derivatives of synephrine, a molecule of natural origin. We synthesized 26 novel compounds from the class of synephrine derivatives and characterized them by HRMS, and <sup>1</sup>H and <sup>13</sup>C NMR. We evaluated <i>in vitro</i> anti-cancer effects in leukemia K562 and lymphoma Granta cells using the MTT assay and studied their potential affinity for the glucocorticoid receptor (GR) <i>in silico</i> using the molecular docking approach. The novel derivative 1-[4-(benzyloxy)phenyl]-2-(hexylamino)ethanol (<b>10S-E2</b>) with the highest GR affinity <i>in silico</i> exhibited cytotoxic activity against K562 and Granta cells after 24 h of treatment at the concentration of approximately 13 µM which correlated with its highest MolDock Score. The other compound with high GR affinity, 2-(hexylamino)-1-(4-nitrophenyl)ethanol (<b>13S-G2</b>), demonstrated cytotoxicity in both cell lines at concentrations of 50–70 µM. Overall, our results may provide a solid rationale for developing and further investigating synephrine derivatives as SEGRAs with anti-cancer activity.https://www.mdpi.com/2218-273X/15/1/2selective glucocorticoid receptor agonistssynephrine derivative synthesisvirtual dockingcytotoxicityhematological malignancies |
| spellingShingle | Ekaterina M. Zhidkova Evgeniya S. Oleynik Ekaterina A. Mikhina Daria V. Stepanycheva Diana D. Grigoreva Lyubov E. Grebenkina Kirill V. Gordeev Ekaterina D. Savina Andrey V. Matveev Marianna G. Yakubovskaya Ekaterina A. Lesovaya Synthesis and Anti-Cancer Activity In Vitro of Synephrine Derivatives Biomolecules selective glucocorticoid receptor agonists synephrine derivative synthesis virtual docking cytotoxicity hematological malignancies |
| title | Synthesis and Anti-Cancer Activity In Vitro of Synephrine Derivatives |
| title_full | Synthesis and Anti-Cancer Activity In Vitro of Synephrine Derivatives |
| title_fullStr | Synthesis and Anti-Cancer Activity In Vitro of Synephrine Derivatives |
| title_full_unstemmed | Synthesis and Anti-Cancer Activity In Vitro of Synephrine Derivatives |
| title_short | Synthesis and Anti-Cancer Activity In Vitro of Synephrine Derivatives |
| title_sort | synthesis and anti cancer activity in vitro of synephrine derivatives |
| topic | selective glucocorticoid receptor agonists synephrine derivative synthesis virtual docking cytotoxicity hematological malignancies |
| url | https://www.mdpi.com/2218-273X/15/1/2 |
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