Glycoconjugation of Betulin Derivatives Using Copper-Catalyzed 1,3-Dipolar Azido-Alkyne Cycloaddition Reaction and a Preliminary Assay of Cytotoxicity of the Obtained Compounds
Pentacyclic lupane-type triterpenoids, such as betulin and its synthetic derivatives, display a broad spectrum of biological activity. However, one of the major drawbacks of these compounds as potential therapeutic agents is their high hydrophobicity and low bioavailability. On the other hand, the p...
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MDPI AG
2020-12-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/25/24/6019 |
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| author | Mirosława Grymel Gabriela Pastuch-Gawołek Anna Lalik Mateusz Zawojak Seweryn Boczek Monika Krawczyk Karol Erfurt |
| author_facet | Mirosława Grymel Gabriela Pastuch-Gawołek Anna Lalik Mateusz Zawojak Seweryn Boczek Monika Krawczyk Karol Erfurt |
| author_sort | Mirosława Grymel |
| collection | DOAJ |
| description | Pentacyclic lupane-type triterpenoids, such as betulin and its synthetic derivatives, display a broad spectrum of biological activity. However, one of the major drawbacks of these compounds as potential therapeutic agents is their high hydrophobicity and low bioavailability. On the other hand, the presence of easily transformable functional groups in the parent structure makes betulin have a high synthetic potential and the ability to form different derivatives. In this context, research on the synthesis of new betulin derivatives as conjugates of naturally occurring triterpenoid with a monosaccharide via a linker containing a heteroaromatic 1,2,3-triazole ring was presented. It has been shown that copper-catalyzed 1,3-dipolar azide-alkyne cycloaddition reaction (CuAAC) provides an easy and effective way to synthesize new molecular hybrids based on natural products. The chemical structures of the obtained betulin glycoconjugates were confirmed by spectroscopic analysis. Cytotoxicity of the obtained compounds was evaluated on a human breast adenocarcinoma cell line (MCF-7) and colorectal carcinoma cell line (HCT 116). The obtained results show that despite the fact that the obtained betulin glycoconjugates do not show interesting antitumor activity, the idea of adding a sugar unit to the betulin backbone may, after some modifications, turn out to be correct and allow for the targeted transport of betulin glycoconjugates into the tumor cells. |
| first_indexed | 2024-03-10T13:56:00Z |
| format | Article |
| id | doaj.art-3bb6896e244c4a2f9ca35965ca83812c |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-10T13:56:00Z |
| publishDate | 2020-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-3bb6896e244c4a2f9ca35965ca83812c2023-11-21T01:36:28ZengMDPI AGMolecules1420-30492020-12-012524601910.3390/molecules25246019Glycoconjugation of Betulin Derivatives Using Copper-Catalyzed 1,3-Dipolar Azido-Alkyne Cycloaddition Reaction and a Preliminary Assay of Cytotoxicity of the Obtained CompoundsMirosława Grymel0Gabriela Pastuch-Gawołek1Anna Lalik2Mateusz Zawojak3Seweryn Boczek4Monika Krawczyk5Karol Erfurt6Department of Organic Chemistry, Bioorganic Chemistry and Biotechnology, Silesian University of Technology, B. Krzywoustego 4, 44-100 Gliwice, PolandDepartment of Organic Chemistry, Bioorganic Chemistry and Biotechnology, Silesian University of Technology, B. Krzywoustego 4, 44-100 Gliwice, PolandBiotechnology Center, Silesian University of Technology, B. Krzywoustego 8, 44-100 Gliwice, PolandDepartment of Organic Chemistry, Bioorganic Chemistry and Biotechnology, Silesian University of Technology, B. Krzywoustego 4, 44-100 Gliwice, PolandDepartment of Organic Chemistry, Bioorganic Chemistry and Biotechnology, Silesian University of Technology, B. Krzywoustego 4, 44-100 Gliwice, PolandDepartment of Organic Chemistry, Bioorganic Chemistry and Biotechnology, Silesian University of Technology, B. Krzywoustego 4, 44-100 Gliwice, PolandDepartment of Chemical Organic Technology and Petrochemistry, Silesian University of Technology, B. Krzywoustego 4, 44-100 Gliwice, PolandPentacyclic lupane-type triterpenoids, such as betulin and its synthetic derivatives, display a broad spectrum of biological activity. However, one of the major drawbacks of these compounds as potential therapeutic agents is their high hydrophobicity and low bioavailability. On the other hand, the presence of easily transformable functional groups in the parent structure makes betulin have a high synthetic potential and the ability to form different derivatives. In this context, research on the synthesis of new betulin derivatives as conjugates of naturally occurring triterpenoid with a monosaccharide via a linker containing a heteroaromatic 1,2,3-triazole ring was presented. It has been shown that copper-catalyzed 1,3-dipolar azide-alkyne cycloaddition reaction (CuAAC) provides an easy and effective way to synthesize new molecular hybrids based on natural products. The chemical structures of the obtained betulin glycoconjugates were confirmed by spectroscopic analysis. Cytotoxicity of the obtained compounds was evaluated on a human breast adenocarcinoma cell line (MCF-7) and colorectal carcinoma cell line (HCT 116). The obtained results show that despite the fact that the obtained betulin glycoconjugates do not show interesting antitumor activity, the idea of adding a sugar unit to the betulin backbone may, after some modifications, turn out to be correct and allow for the targeted transport of betulin glycoconjugates into the tumor cells.https://www.mdpi.com/1420-3049/25/24/6019betulin glycoconjugatesclick chemistry1,3-dipolar cycloadditionanticancer activity |
| spellingShingle | Mirosława Grymel Gabriela Pastuch-Gawołek Anna Lalik Mateusz Zawojak Seweryn Boczek Monika Krawczyk Karol Erfurt Glycoconjugation of Betulin Derivatives Using Copper-Catalyzed 1,3-Dipolar Azido-Alkyne Cycloaddition Reaction and a Preliminary Assay of Cytotoxicity of the Obtained Compounds Molecules betulin glycoconjugates click chemistry 1,3-dipolar cycloaddition anticancer activity |
| title | Glycoconjugation of Betulin Derivatives Using Copper-Catalyzed 1,3-Dipolar Azido-Alkyne Cycloaddition Reaction and a Preliminary Assay of Cytotoxicity of the Obtained Compounds |
| title_full | Glycoconjugation of Betulin Derivatives Using Copper-Catalyzed 1,3-Dipolar Azido-Alkyne Cycloaddition Reaction and a Preliminary Assay of Cytotoxicity of the Obtained Compounds |
| title_fullStr | Glycoconjugation of Betulin Derivatives Using Copper-Catalyzed 1,3-Dipolar Azido-Alkyne Cycloaddition Reaction and a Preliminary Assay of Cytotoxicity of the Obtained Compounds |
| title_full_unstemmed | Glycoconjugation of Betulin Derivatives Using Copper-Catalyzed 1,3-Dipolar Azido-Alkyne Cycloaddition Reaction and a Preliminary Assay of Cytotoxicity of the Obtained Compounds |
| title_short | Glycoconjugation of Betulin Derivatives Using Copper-Catalyzed 1,3-Dipolar Azido-Alkyne Cycloaddition Reaction and a Preliminary Assay of Cytotoxicity of the Obtained Compounds |
| title_sort | glycoconjugation of betulin derivatives using copper catalyzed 1 3 dipolar azido alkyne cycloaddition reaction and a preliminary assay of cytotoxicity of the obtained compounds |
| topic | betulin glycoconjugates click chemistry 1,3-dipolar cycloaddition anticancer activity |
| url | https://www.mdpi.com/1420-3049/25/24/6019 |
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