Molecular Structure, In Vitro Anticancer Study and Molecular Docking of New Phosphate Derivatives of Betulin
A series of 30-diethylphosphate derivatives of betulin were synthesized and evaluated for their in vitro cytotoxic activity against human cancer cell lines, such as amelanotic melanoma (C-32), glioblastoma (SNB-19), and two lines of breast cancer (T47D, MDA-MB-231). The molecular structure and activ...
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doaj-fae6680e9ce44fd584443340ebd3ad672021-02-01T00:02:50ZengMDPI AGMolecules1420-30492021-01-012673773710.3390/molecules26030737Molecular Structure, In Vitro Anticancer Study and Molecular Docking of New Phosphate Derivatives of BetulinElwira Chrobak0Maria Jastrzębska1Ewa Bębenek2Monika Kadela-Tomanek3Krzysztof Marciniec4Małgorzata Latocha5Roman Wrzalik6Joachim Kusz7Stanisław Boryczka8Department of Organic Chemistry, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia, Katowice, 4 Jagiellońska Str., 41-200 Sosnowiec, PolandSilesian Center for Education and Interdisciplinary Research, Institute of Physics, University of Silesia, 75Pułku Piechoty 1a, 41-500 Chorzów, PolandDepartment of Organic Chemistry, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia, Katowice, 4 Jagiellońska Str., 41-200 Sosnowiec, PolandDepartment of Organic Chemistry, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia, Katowice, 4 Jagiellońska Str., 41-200 Sosnowiec, PolandDepartment of Organic Chemistry, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia, Katowice, 4 Jagiellońska Str., 41-200 Sosnowiec, PolandDepartment of Cell Biology, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia, Katowice, 8 Jedności Str., 41-200 Sosnowiec, PolandSilesian Center for Education and Interdisciplinary Research, Institute of Physics, University of Silesia, 75Pułku Piechoty 1a, 41-500 Chorzów, PolandInstitute of Physics, University of Silesia, 75 Pułku Piechoty Str.1a, 41-500 Chorzów, PolandDepartment of Organic Chemistry, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia, Katowice, 4 Jagiellońska Str., 41-200 Sosnowiec, PolandA series of 30-diethylphosphate derivatives of betulin were synthesized and evaluated for their in vitro cytotoxic activity against human cancer cell lines, such as amelanotic melanoma (C-32), glioblastoma (SNB-19), and two lines of breast cancer (T47D, MDA-MB-231). The molecular structure and activities of the new compounds were also compared with their 29-phosphonate analogs. Compounds <b>7a</b> and <b>7b</b> showed the highest activity against C-32 and SNB-19 cell lines. The IC<sub>50</sub> values for <b>7a</b> were 2.15 and 0.91 μM, and, for <b>7b,</b> they were 0.76 and 0.8 μM for the C-32 and SNB-19 lines, respectively. The most potent compounds, <b>7a</b> and <b>7b</b>, were tested for their effects on markers of apoptosis, such as H3, TP53, BAX, and BCL-2. For the whole series of phosphate derivatives, a lipophilicity study was performed, and the ADME parameters were calculated. The most active products were docked to the active site of the EGFR protein. The relative binding affinity of selected phosphate betulin derivatives toward EGFR was compared with standard erlotinib on the basis of ChemScore and K<sub>DEEP</sub> score. Positively, all derivatives docked inside the cavity and showed significant interactions. Moreover, a molecular dynamics study also reveals that ligands <b>7a</b>,<b>b</b> form stable complexes and the plateau phase started after 7 ns.https://www.mdpi.com/1420-3049/26/3/737natural compoundsbetulinanticancer studymolecular dockingEGFR |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Elwira Chrobak Maria Jastrzębska Ewa Bębenek Monika Kadela-Tomanek Krzysztof Marciniec Małgorzata Latocha Roman Wrzalik Joachim Kusz Stanisław Boryczka |
spellingShingle |
Elwira Chrobak Maria Jastrzębska Ewa Bębenek Monika Kadela-Tomanek Krzysztof Marciniec Małgorzata Latocha Roman Wrzalik Joachim Kusz Stanisław Boryczka Molecular Structure, In Vitro Anticancer Study and Molecular Docking of New Phosphate Derivatives of Betulin Molecules natural compounds betulin anticancer study molecular docking EGFR |
author_facet |
Elwira Chrobak Maria Jastrzębska Ewa Bębenek Monika Kadela-Tomanek Krzysztof Marciniec Małgorzata Latocha Roman Wrzalik Joachim Kusz Stanisław Boryczka |
author_sort |
Elwira Chrobak |
title |
Molecular Structure, In Vitro Anticancer Study and Molecular Docking of New Phosphate Derivatives of Betulin |
title_short |
Molecular Structure, In Vitro Anticancer Study and Molecular Docking of New Phosphate Derivatives of Betulin |
title_full |
Molecular Structure, In Vitro Anticancer Study and Molecular Docking of New Phosphate Derivatives of Betulin |
title_fullStr |
Molecular Structure, In Vitro Anticancer Study and Molecular Docking of New Phosphate Derivatives of Betulin |
title_full_unstemmed |
Molecular Structure, In Vitro Anticancer Study and Molecular Docking of New Phosphate Derivatives of Betulin |
title_sort |
molecular structure, in vitro anticancer study and molecular docking of new phosphate derivatives of betulin |
publisher |
MDPI AG |
series |
Molecules |
issn |
1420-3049 |
publishDate |
2021-01-01 |
description |
A series of 30-diethylphosphate derivatives of betulin were synthesized and evaluated for their in vitro cytotoxic activity against human cancer cell lines, such as amelanotic melanoma (C-32), glioblastoma (SNB-19), and two lines of breast cancer (T47D, MDA-MB-231). The molecular structure and activities of the new compounds were also compared with their 29-phosphonate analogs. Compounds <b>7a</b> and <b>7b</b> showed the highest activity against C-32 and SNB-19 cell lines. The IC<sub>50</sub> values for <b>7a</b> were 2.15 and 0.91 μM, and, for <b>7b,</b> they were 0.76 and 0.8 μM for the C-32 and SNB-19 lines, respectively. The most potent compounds, <b>7a</b> and <b>7b</b>, were tested for their effects on markers of apoptosis, such as H3, TP53, BAX, and BCL-2. For the whole series of phosphate derivatives, a lipophilicity study was performed, and the ADME parameters were calculated. The most active products were docked to the active site of the EGFR protein. The relative binding affinity of selected phosphate betulin derivatives toward EGFR was compared with standard erlotinib on the basis of ChemScore and K<sub>DEEP</sub> score. Positively, all derivatives docked inside the cavity and showed significant interactions. Moreover, a molecular dynamics study also reveals that ligands <b>7a</b>,<b>b</b> form stable complexes and the plateau phase started after 7 ns. |
topic |
natural compounds betulin anticancer study molecular docking EGFR |
url |
https://www.mdpi.com/1420-3049/26/3/737 |
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