Design and Synthesis of Novel Podophyllotoxins Hybrids and the Effects of Different Functional Groups on Cytotoxicity
Development of novel anticancer therapeutic candidates is one of the key challenges in medicinal chemistry. Podophyllotoxin and its derivatives, as a potent cytotoxic agent, have been at the center of extensive chemical amendment and pharmacological investigation. Herein, a new series of podophyllot...
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| Format: | Article |
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MDPI AG
2021-12-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/27/1/220 |
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| author | Zhongtao Yang Zitong Zhou Xiai Luo Xiaoling Luo Hui Luo Lianxiang Luo Weiguang Yang |
| author_facet | Zhongtao Yang Zitong Zhou Xiai Luo Xiaoling Luo Hui Luo Lianxiang Luo Weiguang Yang |
| author_sort | Zhongtao Yang |
| collection | DOAJ |
| description | Development of novel anticancer therapeutic candidates is one of the key challenges in medicinal chemistry. Podophyllotoxin and its derivatives, as a potent cytotoxic agent, have been at the center of extensive chemical amendment and pharmacological investigation. Herein, a new series of podophyllotoxin-<i>N</i>-sulfonyl amidine hybrids (<b>4a</b>–<b>4v</b>, <b>5a</b>–<b>5f</b>) were synthesized by a CuAAC/ring-opening procedure. All the synthesized podophyllotoxins derivatives were evaluated for in vitro cytotoxic activity against a panel of human lung (A-549) cancer cell lines. Different substituents’, or functional groups’ antiproliferative activities were discussed. The –CF<sub>3</sub> group performed best (IC<sub>50</sub>: 1.65 μM) and exhibited more potent activity than etoposide. Furthermore, molecular docking and dynamics studies were also conducted for active compounds and the results were in good agreement with the observed IC<sub>50</sub> values. |
| first_indexed | 2024-03-10T03:29:37Z |
| format | Article |
| id | doaj.art-1cc4659ea80849aa951a8bfd1cb7b197 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-10T03:29:37Z |
| publishDate | 2021-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-1cc4659ea80849aa951a8bfd1cb7b1972023-11-23T11:58:29ZengMDPI AGMolecules1420-30492021-12-0127122010.3390/molecules27010220Design and Synthesis of Novel Podophyllotoxins Hybrids and the Effects of Different Functional Groups on CytotoxicityZhongtao Yang0Zitong Zhou1Xiai Luo2Xiaoling Luo3Hui Luo4Lianxiang Luo5Weiguang Yang6The Marine Biomedical Research Institute, Guangdong Medical University, Zhanjiang 524023, ChinaThe Marine Biomedical Research Institute, Guangdong Medical University, Zhanjiang 524023, ChinaThe Marine Biomedical Research Institute, Guangdong Medical University, Zhanjiang 524023, ChinaSchool of Basic Medical Sciences, Guangxi Medical University, Nanning 530021, ChinaThe Marine Biomedical Research Institute, Guangdong Medical University, Zhanjiang 524023, ChinaThe Marine Biomedical Research Institute, Guangdong Medical University, Zhanjiang 524023, ChinaThe Marine Biomedical Research Institute, Guangdong Medical University, Zhanjiang 524023, ChinaDevelopment of novel anticancer therapeutic candidates is one of the key challenges in medicinal chemistry. Podophyllotoxin and its derivatives, as a potent cytotoxic agent, have been at the center of extensive chemical amendment and pharmacological investigation. Herein, a new series of podophyllotoxin-<i>N</i>-sulfonyl amidine hybrids (<b>4a</b>–<b>4v</b>, <b>5a</b>–<b>5f</b>) were synthesized by a CuAAC/ring-opening procedure. All the synthesized podophyllotoxins derivatives were evaluated for in vitro cytotoxic activity against a panel of human lung (A-549) cancer cell lines. Different substituents’, or functional groups’ antiproliferative activities were discussed. The –CF<sub>3</sub> group performed best (IC<sub>50</sub>: 1.65 μM) and exhibited more potent activity than etoposide. Furthermore, molecular docking and dynamics studies were also conducted for active compounds and the results were in good agreement with the observed IC<sub>50</sub> values.https://www.mdpi.com/1420-3049/27/1/220podophyllotoxin hybridsCuAACantiproliferative activitymolecular dockingmolecular dynamicsstructure–activity correlation |
| spellingShingle | Zhongtao Yang Zitong Zhou Xiai Luo Xiaoling Luo Hui Luo Lianxiang Luo Weiguang Yang Design and Synthesis of Novel Podophyllotoxins Hybrids and the Effects of Different Functional Groups on Cytotoxicity Molecules podophyllotoxin hybrids CuAAC antiproliferative activity molecular docking molecular dynamics structure–activity correlation |
| title | Design and Synthesis of Novel Podophyllotoxins Hybrids and the Effects of Different Functional Groups on Cytotoxicity |
| title_full | Design and Synthesis of Novel Podophyllotoxins Hybrids and the Effects of Different Functional Groups on Cytotoxicity |
| title_fullStr | Design and Synthesis of Novel Podophyllotoxins Hybrids and the Effects of Different Functional Groups on Cytotoxicity |
| title_full_unstemmed | Design and Synthesis of Novel Podophyllotoxins Hybrids and the Effects of Different Functional Groups on Cytotoxicity |
| title_short | Design and Synthesis of Novel Podophyllotoxins Hybrids and the Effects of Different Functional Groups on Cytotoxicity |
| title_sort | design and synthesis of novel podophyllotoxins hybrids and the effects of different functional groups on cytotoxicity |
| topic | podophyllotoxin hybrids CuAAC antiproliferative activity molecular docking molecular dynamics structure–activity correlation |
| url | https://www.mdpi.com/1420-3049/27/1/220 |
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