Betulinic Acid Decorated with Polar Groups and Blue Emitting BODIPY Dye: Synthesis, Cytotoxicity, Cell-Cycle Analysis and Anti-HIV Profiling
Betulinic acid (BA) is a potent triterpene, which has shown promising potential in cancer and HIV-1 treatment. Here, we report a synthesis and biological evaluation of 17 new compounds, including BODIPY labelled analogues derived from BA. The analogues terminated by amino moiety showed increased cyt...
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MDPI AG
2021-08-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/9/9/1104 |
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| author | David Kodr Jarmila Stanková Michaela Rumlová Petr Džubák Jiří Řehulka Tomáš Zimmermann Ivana Křížová Soňa Gurská Marián Hajdúch Pavel B. Drašar Michal Jurášek |
| author_facet | David Kodr Jarmila Stanková Michaela Rumlová Petr Džubák Jiří Řehulka Tomáš Zimmermann Ivana Křížová Soňa Gurská Marián Hajdúch Pavel B. Drašar Michal Jurášek |
| author_sort | David Kodr |
| collection | DOAJ |
| description | Betulinic acid (BA) is a potent triterpene, which has shown promising potential in cancer and HIV-1 treatment. Here, we report a synthesis and biological evaluation of 17 new compounds, including BODIPY labelled analogues derived from BA. The analogues terminated by amino moiety showed increased cytotoxicity (e.g., BA had on CCRF-CEM IC<sub>50</sub> > 50 μM, amine <b>3</b> IC<sub>50</sub> 0.21 and amine <b>14</b> IC<sub>50</sub> 0.29). The cell-cycle arrest was evaluated and did not show general features for all the tested compounds. A fluorescence microscopy study of six derivatives revealed that only <b>4</b> and <b>6</b> were detected in living cells. These compounds were colocalized with the endoplasmic reticulum and mitochondria, indicating possible targets in these organelles. The study of anti-HIV-1 activity showed that <b>8</b>, <b>10</b>, <b>16</b>, <b>17</b> and <b>18</b> have had IC<sub>50i</sub> > 10 μM. Only completely processed p24 CA was identified in the viruses formed in the presence of compounds <b>4</b> and <b>12</b>. In the cases of <b>2</b>, <b>8</b>, <b>9</b>, <b>10</b>, <b>16</b>, <b>17</b> and <b>18</b>, we identified not fully processed p24 CA and p25 CA-SP1 protein. This observation suggests a similar mechanism of inhibition as described for bevirimat. |
| first_indexed | 2024-03-10T07:53:13Z |
| format | Article |
| id | doaj.art-5e863bb72c9b49ad97b6593f6a49c8e3 |
| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-10T07:53:13Z |
| publishDate | 2021-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj.art-5e863bb72c9b49ad97b6593f6a49c8e32023-11-22T12:07:04ZengMDPI AGBiomedicines2227-90592021-08-0199110410.3390/biomedicines9091104Betulinic Acid Decorated with Polar Groups and Blue Emitting BODIPY Dye: Synthesis, Cytotoxicity, Cell-Cycle Analysis and Anti-HIV ProfilingDavid Kodr0Jarmila Stanková1Michaela Rumlová2Petr Džubák3Jiří Řehulka4Tomáš Zimmermann5Ivana Křížová6Soňa Gurská7Marián Hajdúch8Pavel B. Drašar9Michal Jurášek10Department of Chemistry of Natural Compounds, University of Chemistry and Technology Prague, 16628 Prague, Czech RepublicInstitute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacký University and University Hospital in Olomouc, 77900 Olomouc, Czech RepublicDepartment of Biotechnology, University of Chemistry and Technology Prague, 16628 Prague, Czech RepublicInstitute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacký University and University Hospital in Olomouc, 77900 Olomouc, Czech RepublicInstitute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacký University and University Hospital in Olomouc, 77900 Olomouc, Czech RepublicDepartment of Chemistry of Natural Compounds, University of Chemistry and Technology Prague, 16628 Prague, Czech RepublicDepartment of Biotechnology, University of Chemistry and Technology Prague, 16628 Prague, Czech RepublicInstitute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacký University and University Hospital in Olomouc, 77900 Olomouc, Czech RepublicInstitute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacký University and University Hospital in Olomouc, 77900 Olomouc, Czech RepublicDepartment of Chemistry of Natural Compounds, University of Chemistry and Technology Prague, 16628 Prague, Czech RepublicDepartment of Chemistry of Natural Compounds, University of Chemistry and Technology Prague, 16628 Prague, Czech RepublicBetulinic acid (BA) is a potent triterpene, which has shown promising potential in cancer and HIV-1 treatment. Here, we report a synthesis and biological evaluation of 17 new compounds, including BODIPY labelled analogues derived from BA. The analogues terminated by amino moiety showed increased cytotoxicity (e.g., BA had on CCRF-CEM IC<sub>50</sub> > 50 μM, amine <b>3</b> IC<sub>50</sub> 0.21 and amine <b>14</b> IC<sub>50</sub> 0.29). The cell-cycle arrest was evaluated and did not show general features for all the tested compounds. A fluorescence microscopy study of six derivatives revealed that only <b>4</b> and <b>6</b> were detected in living cells. These compounds were colocalized with the endoplasmic reticulum and mitochondria, indicating possible targets in these organelles. The study of anti-HIV-1 activity showed that <b>8</b>, <b>10</b>, <b>16</b>, <b>17</b> and <b>18</b> have had IC<sub>50i</sub> > 10 μM. Only completely processed p24 CA was identified in the viruses formed in the presence of compounds <b>4</b> and <b>12</b>. In the cases of <b>2</b>, <b>8</b>, <b>9</b>, <b>10</b>, <b>16</b>, <b>17</b> and <b>18</b>, we identified not fully processed p24 CA and p25 CA-SP1 protein. This observation suggests a similar mechanism of inhibition as described for bevirimat.https://www.mdpi.com/2227-9059/9/9/1104betulinic acidBODIPYbevirimatcytotoxicitycancercell-cycle |
| spellingShingle | David Kodr Jarmila Stanková Michaela Rumlová Petr Džubák Jiří Řehulka Tomáš Zimmermann Ivana Křížová Soňa Gurská Marián Hajdúch Pavel B. Drašar Michal Jurášek Betulinic Acid Decorated with Polar Groups and Blue Emitting BODIPY Dye: Synthesis, Cytotoxicity, Cell-Cycle Analysis and Anti-HIV Profiling Biomedicines betulinic acid BODIPY bevirimat cytotoxicity cancer cell-cycle |
| title | Betulinic Acid Decorated with Polar Groups and Blue Emitting BODIPY Dye: Synthesis, Cytotoxicity, Cell-Cycle Analysis and Anti-HIV Profiling |
| title_full | Betulinic Acid Decorated with Polar Groups and Blue Emitting BODIPY Dye: Synthesis, Cytotoxicity, Cell-Cycle Analysis and Anti-HIV Profiling |
| title_fullStr | Betulinic Acid Decorated with Polar Groups and Blue Emitting BODIPY Dye: Synthesis, Cytotoxicity, Cell-Cycle Analysis and Anti-HIV Profiling |
| title_full_unstemmed | Betulinic Acid Decorated with Polar Groups and Blue Emitting BODIPY Dye: Synthesis, Cytotoxicity, Cell-Cycle Analysis and Anti-HIV Profiling |
| title_short | Betulinic Acid Decorated with Polar Groups and Blue Emitting BODIPY Dye: Synthesis, Cytotoxicity, Cell-Cycle Analysis and Anti-HIV Profiling |
| title_sort | betulinic acid decorated with polar groups and blue emitting bodipy dye synthesis cytotoxicity cell cycle analysis and anti hiv profiling |
| topic | betulinic acid BODIPY bevirimat cytotoxicity cancer cell-cycle |
| url | https://www.mdpi.com/2227-9059/9/9/1104 |
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