Structure–Activity Relationship of the Thiacalix[4]arenes Family with Sulfobetaine Fragments: Self-Assembly and Cytotoxic Effect against Cancer Cell Lines
Regulating the structure of macrocyclic host molecules and supramolecular assemblies is crucial because the structure–activity relationship often plays a role in governing the properties of these systems. Herein, we propose and develop an approach to the synthesis of the family of sulfobetaine funct...
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| Format: | Article |
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MDPI AG
2022-02-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/27/4/1364 |
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| author | Luidmila Yakimova Aisylu Kunafina Aigul Nugmanova Pavel Padnya Alexandra Voloshina Konstantin Petrov Ivan Stoikov |
| author_facet | Luidmila Yakimova Aisylu Kunafina Aigul Nugmanova Pavel Padnya Alexandra Voloshina Konstantin Petrov Ivan Stoikov |
| author_sort | Luidmila Yakimova |
| collection | DOAJ |
| description | Regulating the structure of macrocyclic host molecules and supramolecular assemblies is crucial because the structure–activity relationship often plays a role in governing the properties of these systems. Herein, we propose and develop an approach to the synthesis of the family of sulfobetaine functionalized thiacalix[4]arenes with regulation of the self-assembly and cytotoxic effect against cancer cell lines. The dynamic light scattering method showed that the synthesized macrocycles in <i>cone</i>, <i>partial cone</i> and <i>1,3-alternate</i> conformations form submicron-sized particles with Ag<sup>+</sup> in water, but the particle size and polydispersity of the systems studied depend on the macrocycle conformation. Based on the results obtained by <sup>1</sup>H and <sup>1</sup>H-<sup>1</sup>H NOESY NMR spectroscopy and transmission electron microscopy for the macrocycles and their aggregates with Ag<sup>+</sup>, a coordination scheme for the Ag<sup>+</sup> and different conformations of <i>p</i>-<i>tert</i>-butylthiacalix[4]arene functionalized with sulfobetaine fragments was proposed. The type of coordination determines the different shapes of the associates. Cytotoxic properties are shown to be controlled by the shape of associates, with the highest activity demonstrated by thiacalix[4]arenes in <i>partial</i> <i>cone</i> conformation. This complex <i>partial cone</i>/Ag<sup>+</sup> is two times higher than the reference drug imatinib mesylate. High selectivity against cervical carcinoma cell line indicates the prospect of their using as components of new anticancer system. |
| first_indexed | 2024-03-09T21:20:32Z |
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| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-09T21:20:32Z |
| publishDate | 2022-02-01 |
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| record_format | Article |
| series | Molecules |
| spelling | doaj.art-20d852dce9fc447bb709e31a723322cb2023-11-23T21:22:51ZengMDPI AGMolecules1420-30492022-02-01274136410.3390/molecules27041364Structure–Activity Relationship of the Thiacalix[4]arenes Family with Sulfobetaine Fragments: Self-Assembly and Cytotoxic Effect against Cancer Cell LinesLuidmila Yakimova0Aisylu Kunafina1Aigul Nugmanova2Pavel Padnya3Alexandra Voloshina4Konstantin Petrov5Ivan Stoikov6A.M. Butlerov’ Chemistry Institute, Kazan Federal University, 18 Kremlevskaya Street, 420008 Kazan, RussiaA.M. Butlerov’ Chemistry Institute, Kazan Federal University, 18 Kremlevskaya Street, 420008 Kazan, RussiaA.M. Butlerov’ Chemistry Institute, Kazan Federal University, 18 Kremlevskaya Street, 420008 Kazan, RussiaA.M. Butlerov’ Chemistry Institute, Kazan Federal University, 18 Kremlevskaya Street, 420008 Kazan, RussiaArbuzov Institute of Organic and Physical Chemistry, FRC Kazan Scientific Center of RAS, 8 Arbuzov Street, 420088 Kazan, RussiaArbuzov Institute of Organic and Physical Chemistry, FRC Kazan Scientific Center of RAS, 8 Arbuzov Street, 420088 Kazan, RussiaA.M. Butlerov’ Chemistry Institute, Kazan Federal University, 18 Kremlevskaya Street, 420008 Kazan, RussiaRegulating the structure of macrocyclic host molecules and supramolecular assemblies is crucial because the structure–activity relationship often plays a role in governing the properties of these systems. Herein, we propose and develop an approach to the synthesis of the family of sulfobetaine functionalized thiacalix[4]arenes with regulation of the self-assembly and cytotoxic effect against cancer cell lines. The dynamic light scattering method showed that the synthesized macrocycles in <i>cone</i>, <i>partial cone</i> and <i>1,3-alternate</i> conformations form submicron-sized particles with Ag<sup>+</sup> in water, but the particle size and polydispersity of the systems studied depend on the macrocycle conformation. Based on the results obtained by <sup>1</sup>H and <sup>1</sup>H-<sup>1</sup>H NOESY NMR spectroscopy and transmission electron microscopy for the macrocycles and their aggregates with Ag<sup>+</sup>, a coordination scheme for the Ag<sup>+</sup> and different conformations of <i>p</i>-<i>tert</i>-butylthiacalix[4]arene functionalized with sulfobetaine fragments was proposed. The type of coordination determines the different shapes of the associates. Cytotoxic properties are shown to be controlled by the shape of associates, with the highest activity demonstrated by thiacalix[4]arenes in <i>partial</i> <i>cone</i> conformation. This complex <i>partial cone</i>/Ag<sup>+</sup> is two times higher than the reference drug imatinib mesylate. High selectivity against cervical carcinoma cell line indicates the prospect of their using as components of new anticancer system.https://www.mdpi.com/1420-3049/27/4/1364sulfobetainesthiacalixareneself-assemblysilver ionscytotoxicitycancer cell lines |
| spellingShingle | Luidmila Yakimova Aisylu Kunafina Aigul Nugmanova Pavel Padnya Alexandra Voloshina Konstantin Petrov Ivan Stoikov Structure–Activity Relationship of the Thiacalix[4]arenes Family with Sulfobetaine Fragments: Self-Assembly and Cytotoxic Effect against Cancer Cell Lines Molecules sulfobetaines thiacalixarene self-assembly silver ions cytotoxicity cancer cell lines |
| title | Structure–Activity Relationship of the Thiacalix[4]arenes Family with Sulfobetaine Fragments: Self-Assembly and Cytotoxic Effect against Cancer Cell Lines |
| title_full | Structure–Activity Relationship of the Thiacalix[4]arenes Family with Sulfobetaine Fragments: Self-Assembly and Cytotoxic Effect against Cancer Cell Lines |
| title_fullStr | Structure–Activity Relationship of the Thiacalix[4]arenes Family with Sulfobetaine Fragments: Self-Assembly and Cytotoxic Effect against Cancer Cell Lines |
| title_full_unstemmed | Structure–Activity Relationship of the Thiacalix[4]arenes Family with Sulfobetaine Fragments: Self-Assembly and Cytotoxic Effect against Cancer Cell Lines |
| title_short | Structure–Activity Relationship of the Thiacalix[4]arenes Family with Sulfobetaine Fragments: Self-Assembly and Cytotoxic Effect against Cancer Cell Lines |
| title_sort | structure activity relationship of the thiacalix 4 arenes family with sulfobetaine fragments self assembly and cytotoxic effect against cancer cell lines |
| topic | sulfobetaines thiacalixarene self-assembly silver ions cytotoxicity cancer cell lines |
| url | https://www.mdpi.com/1420-3049/27/4/1364 |
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