Synthesis of Oleanolic Acid-Dithiocarbamate Conjugates and Evaluation of Their Broad-Spectrum Antitumor Activities
Efficient and mild synthetic routes for bioactive natural product derivatives are of current interest for drug discovery. Herein, on the basis of the pharmacophore hybrid strategy, we report a two-step protocol to obtain a series of structurally novel oleanolic acid (OA)-dithiocarbamate conjugates i...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-02-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/28/3/1414 |
| _version_ | 1797623709263986688 |
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| author | Liyao Tang Yan Zhang Jinrun Xu Qingfan Yang Fukuan Du Xu Wu Mingxing Li Jing Shen Shuai Deng Yueshui Zhao Zhangang Xiao Yu Chen |
| author_facet | Liyao Tang Yan Zhang Jinrun Xu Qingfan Yang Fukuan Du Xu Wu Mingxing Li Jing Shen Shuai Deng Yueshui Zhao Zhangang Xiao Yu Chen |
| author_sort | Liyao Tang |
| collection | DOAJ |
| description | Efficient and mild synthetic routes for bioactive natural product derivatives are of current interest for drug discovery. Herein, on the basis of the pharmacophore hybrid strategy, we report a two-step protocol to obtain a series of structurally novel oleanolic acid (OA)-dithiocarbamate conjugates in mild conditions with high yields. Moreover, biological evaluations indicated that representative compound <b>3e</b> exhibited the most potent and broad-spectrum antiproliferative effects against Panc1, A549, Hep3B, Huh-7, HT-29, and Hela cells with low cytotoxicity on normal cells. In terms of the IC<sub>50</sub> values, these OA-dithiocarbamate conjugates were up to 30-fold more potent than the natural product OA. These compounds may be promising hit compounds for the development of novel anti-cancer drugs. |
| first_indexed | 2024-03-11T09:32:39Z |
| format | Article |
| id | doaj.art-ad2918875594452b896216327856d536 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-11T09:32:39Z |
| publishDate | 2023-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-ad2918875594452b896216327856d5362023-11-16T17:32:10ZengMDPI AGMolecules1420-30492023-02-01283141410.3390/molecules28031414Synthesis of Oleanolic Acid-Dithiocarbamate Conjugates and Evaluation of Their Broad-Spectrum Antitumor ActivitiesLiyao Tang0Yan Zhang1Jinrun Xu2Qingfan Yang3Fukuan Du4Xu Wu5Mingxing Li6Jing Shen7Shuai Deng8Yueshui Zhao9Zhangang Xiao10Yu Chen11Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou 646000, ChinaLaboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou 646000, ChinaLaboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou 646000, ChinaDepartment of Oncology, The Affiliated Hospital of Southwest Medical University, Southwest Medical University, Luzhou 646000, ChinaLaboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou 646000, ChinaLaboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou 646000, ChinaLaboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou 646000, ChinaLaboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou 646000, ChinaLaboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou 646000, ChinaLaboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou 646000, ChinaDepartment of Oncology, The Affiliated Hospital of Southwest Medical University, Southwest Medical University, Luzhou 646000, ChinaLaboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou 646000, ChinaEfficient and mild synthetic routes for bioactive natural product derivatives are of current interest for drug discovery. Herein, on the basis of the pharmacophore hybrid strategy, we report a two-step protocol to obtain a series of structurally novel oleanolic acid (OA)-dithiocarbamate conjugates in mild conditions with high yields. Moreover, biological evaluations indicated that representative compound <b>3e</b> exhibited the most potent and broad-spectrum antiproliferative effects against Panc1, A549, Hep3B, Huh-7, HT-29, and Hela cells with low cytotoxicity on normal cells. In terms of the IC<sub>50</sub> values, these OA-dithiocarbamate conjugates were up to 30-fold more potent than the natural product OA. These compounds may be promising hit compounds for the development of novel anti-cancer drugs.https://www.mdpi.com/1420-3049/28/3/1414structural modificationoleanolic acidnatural product derivativedithiocarbamatehybrid strategyantitumor activity |
| spellingShingle | Liyao Tang Yan Zhang Jinrun Xu Qingfan Yang Fukuan Du Xu Wu Mingxing Li Jing Shen Shuai Deng Yueshui Zhao Zhangang Xiao Yu Chen Synthesis of Oleanolic Acid-Dithiocarbamate Conjugates and Evaluation of Their Broad-Spectrum Antitumor Activities Molecules structural modification oleanolic acid natural product derivative dithiocarbamate hybrid strategy antitumor activity |
| title | Synthesis of Oleanolic Acid-Dithiocarbamate Conjugates and Evaluation of Their Broad-Spectrum Antitumor Activities |
| title_full | Synthesis of Oleanolic Acid-Dithiocarbamate Conjugates and Evaluation of Their Broad-Spectrum Antitumor Activities |
| title_fullStr | Synthesis of Oleanolic Acid-Dithiocarbamate Conjugates and Evaluation of Their Broad-Spectrum Antitumor Activities |
| title_full_unstemmed | Synthesis of Oleanolic Acid-Dithiocarbamate Conjugates and Evaluation of Their Broad-Spectrum Antitumor Activities |
| title_short | Synthesis of Oleanolic Acid-Dithiocarbamate Conjugates and Evaluation of Their Broad-Spectrum Antitumor Activities |
| title_sort | synthesis of oleanolic acid dithiocarbamate conjugates and evaluation of their broad spectrum antitumor activities |
| topic | structural modification oleanolic acid natural product derivative dithiocarbamate hybrid strategy antitumor activity |
| url | https://www.mdpi.com/1420-3049/28/3/1414 |
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