Betulinic Acid Decorated with Polar Groups and Blue Emitting BODIPY Dye: Synthesis, Cytotoxicity, Cell-Cycle Analysis and Anti-HIV Profiling

oleh: David Kodr, Jarmila Stanková, Michaela Rumlová, Petr Džubák, Jiří Řehulka, Tomáš Zimmermann, Ivana Křížová, Soňa Gurská, Marián Hajdúch, Pavel B. Drašar, Michal Jurášek

Format: Article
Diterbitkan: MDPI AG 2021-08-01

Deskripsi

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.