Design, Synthesis of Novel Tetrandrine-14-<span style="font-variant: small-caps">l</span>-Amino Acid and Tetrandrine-14-<span style="font-variant: small-caps">l</span>-Amino Acid-Urea Derivatives as Potential Anti-Cancer Agents
Tetrandrine, a dibenzyltetrahydroisoquinoline alkaloid isolated from the root of the traditional Chinese medicinal plant <i>Stephania tetrandra</i> S. Moore, a member of the Menispermaceae, showed anti-cancer activity by inhibiting cell proliferation, preventing cell cycle progress and i...
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| Format: | Article |
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MDPI AG
2020-04-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/25/7/1738 |
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| author | Sheng-Cao Hu Jin Yang Chao Chen Jun-Rong Song Wei-Dong Pan |
| author_facet | Sheng-Cao Hu Jin Yang Chao Chen Jun-Rong Song Wei-Dong Pan |
| author_sort | Sheng-Cao Hu |
| collection | DOAJ |
| description | Tetrandrine, a dibenzyltetrahydroisoquinoline alkaloid isolated from the root of the traditional Chinese medicinal plant <i>Stephania tetrandra</i> S. Moore, a member of the Menispermaceae, showed anti-cancer activity by inhibiting cell proliferation, preventing cell cycle progress and induction of cell death and autophagy. In this study, twelve tetrandrine-<span style="font-variant: small-caps;">l</span>-amino acid derivatives and twelve tetrandrine-14-<span style="font-variant: small-caps;">l</span>-amino acid-urea derivatives were designed and synthesized, using C14-aminotetrandrine as raw material. Then the preliminary in vitro anti-cancer activities of these derivatives against human breast cancer cell line MDA-MB-231, human leukemia cell lines HEL and K562 were evaluated. The in vitro cytotoxicity results showed that these derivatives exhibited potent inhibitory effects on cancer cell growth, and the primary structure-activity relationships were evaluated. Notably, compound <b>3f</b> exhibited satisfactory anticancer activity against all three cancer cell lines, especially the HEL cell line, with the IC<sub>50</sub> value of 0.23 µM. Further research showed that <b>3f</b> could induce G1/S cycle arrest and apoptosis in a dose- and time- dependent manner on the leukemia cell line HEL. The results suggested that <b>3f</b> may be used as a potential anti-cancer agent for human leukemia. |
| first_indexed | 2024-03-10T20:33:57Z |
| format | Article |
| id | doaj.art-78e4c69926994bc2bd4b3ec72e1e6a2e |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-10T20:33:57Z |
| publishDate | 2020-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-78e4c69926994bc2bd4b3ec72e1e6a2e2023-11-19T21:09:48ZengMDPI AGMolecules1420-30492020-04-01257173810.3390/molecules25071738Design, Synthesis of Novel Tetrandrine-14-<span style="font-variant: small-caps">l</span>-Amino Acid and Tetrandrine-14-<span style="font-variant: small-caps">l</span>-Amino Acid-Urea Derivatives as Potential Anti-Cancer AgentsSheng-Cao Hu0Jin Yang1Chao Chen2Jun-Rong Song3Wei-Dong Pan4College of Pharmacy, Zunyi Medical University, Zunyi 563000, ChinaCollege of Pharmacy, Zunyi Medical University, Zunyi 563000, ChinaState Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang 550014, ChinaState Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang 550014, ChinaCollege of Pharmacy, Zunyi Medical University, Zunyi 563000, ChinaTetrandrine, a dibenzyltetrahydroisoquinoline alkaloid isolated from the root of the traditional Chinese medicinal plant <i>Stephania tetrandra</i> S. Moore, a member of the Menispermaceae, showed anti-cancer activity by inhibiting cell proliferation, preventing cell cycle progress and induction of cell death and autophagy. In this study, twelve tetrandrine-<span style="font-variant: small-caps;">l</span>-amino acid derivatives and twelve tetrandrine-14-<span style="font-variant: small-caps;">l</span>-amino acid-urea derivatives were designed and synthesized, using C14-aminotetrandrine as raw material. Then the preliminary in vitro anti-cancer activities of these derivatives against human breast cancer cell line MDA-MB-231, human leukemia cell lines HEL and K562 were evaluated. The in vitro cytotoxicity results showed that these derivatives exhibited potent inhibitory effects on cancer cell growth, and the primary structure-activity relationships were evaluated. Notably, compound <b>3f</b> exhibited satisfactory anticancer activity against all three cancer cell lines, especially the HEL cell line, with the IC<sub>50</sub> value of 0.23 µM. Further research showed that <b>3f</b> could induce G1/S cycle arrest and apoptosis in a dose- and time- dependent manner on the leukemia cell line HEL. The results suggested that <b>3f</b> may be used as a potential anti-cancer agent for human leukemia.https://www.mdpi.com/1420-3049/25/7/1738tetrandrine derivatives<span style="font-variant: small-caps">l</span>-amino acidureaanti-cancer activity |
| spellingShingle | Sheng-Cao Hu Jin Yang Chao Chen Jun-Rong Song Wei-Dong Pan Design, Synthesis of Novel Tetrandrine-14-<span style="font-variant: small-caps">l</span>-Amino Acid and Tetrandrine-14-<span style="font-variant: small-caps">l</span>-Amino Acid-Urea Derivatives as Potential Anti-Cancer Agents Molecules tetrandrine derivatives <span style="font-variant: small-caps">l</span>-amino acid urea anti-cancer activity |
| title | Design, Synthesis of Novel Tetrandrine-14-<span style="font-variant: small-caps">l</span>-Amino Acid and Tetrandrine-14-<span style="font-variant: small-caps">l</span>-Amino Acid-Urea Derivatives as Potential Anti-Cancer Agents |
| title_full | Design, Synthesis of Novel Tetrandrine-14-<span style="font-variant: small-caps">l</span>-Amino Acid and Tetrandrine-14-<span style="font-variant: small-caps">l</span>-Amino Acid-Urea Derivatives as Potential Anti-Cancer Agents |
| title_fullStr | Design, Synthesis of Novel Tetrandrine-14-<span style="font-variant: small-caps">l</span>-Amino Acid and Tetrandrine-14-<span style="font-variant: small-caps">l</span>-Amino Acid-Urea Derivatives as Potential Anti-Cancer Agents |
| title_full_unstemmed | Design, Synthesis of Novel Tetrandrine-14-<span style="font-variant: small-caps">l</span>-Amino Acid and Tetrandrine-14-<span style="font-variant: small-caps">l</span>-Amino Acid-Urea Derivatives as Potential Anti-Cancer Agents |
| title_short | Design, Synthesis of Novel Tetrandrine-14-<span style="font-variant: small-caps">l</span>-Amino Acid and Tetrandrine-14-<span style="font-variant: small-caps">l</span>-Amino Acid-Urea Derivatives as Potential Anti-Cancer Agents |
| title_sort | design synthesis of novel tetrandrine 14 span style font variant small caps l span amino acid and tetrandrine 14 span style font variant small caps l span amino acid urea derivatives as potential anti cancer agents |
| topic | tetrandrine derivatives <span style="font-variant: small-caps">l</span>-amino acid urea anti-cancer activity |
| url | https://www.mdpi.com/1420-3049/25/7/1738 |
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