N-Alkylation of Anthracycline Antibiotics by Natural Sesquiterpene Lactones as a Way to Obtain Antitumor Agents with Reduced Side Effects
| Autor: | A. V. Semakov, Yulia R. Aleksandrova, Sergey G. Klochkov, Ekaterina Yandulova, Margarita E. Neganova, Lada V. Anikina, S. A. Pukhov |
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| Rok vydání: | 2021 |
| Předmět: |
conjugates
0301 basic medicine Anthracycline QH301-705.5 Daunorubicin cardiotoxicity Medicine (miscellaneous) Pharmacology Sesquiterpene doxorubicin Article General Biochemistry Genetics and Molecular Biology 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine sesquiterpene lactones medicine cancer Doxorubicin Biology (General) Cytotoxicity Cardiotoxicity Biological activity glycolysis 030104 developmental biology daunorubicin chemistry 030220 oncology & carcinogenesis Toxicity rat heart mitochondria medicine.drug |
| Zdroj: | Biomedicines, Vol 9, Iss 547, p 547 (2021) Biomedicines Volume 9 Issue 5 |
| ISSN: | 2227-9059 |
| DOI: | 10.3390/biomedicines9050547 |
| Popis: | Anthracycline antitumor antibiotics are one of the promising classes of chemotherapeutic agents for cancer treatment. The main deterrent to their use is high toxicity to a healthy environment, including cumulative cardiotoxicity. In our work, bipharmacophore molecules containing in their structure a fragment of the known anthracycline antibiotics daunorubicin and doxorubicin and natural sesquiterpene lactones were obtained for the first time. When studying the biological activity of the synthesized compounds, it was found that with equal and, in some cases, higher cytotoxicity and glycolysis inhibition by anthracycline antibiotics conjugates with sesquiterpene lactones in comparison with doxo- and daunorubicin, a reduced damaging effect on the functioning of rat heart mitochondria was observed. The results obtained allow us to confirm the assumption that the chemical modification of the anthracycline antibiotics molecules doxo- and daunorubicin by natural sesquiterpene lactones can be a promising strategy for creating potential antitumor chemotherapeutic drugs with a pronounced cytotoxic effect on tumor cells and a reduced damaging effect on healthy cells of the human organism. |
| Databáze: | OpenAIRE |
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