Discovery of 29-O-acyl-toosendanin-based derivatives as potent anti-cancer agents
Structural modification of natural products is an effective strategy to discover potent lead compounds with improved medicinal performance. Toosendanin (TSN), a natural limonoid with diverse pharmacological properties, was selected as the starting material for structural modification to obtain more...
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| Format: | Article |
| Language: | English |
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Elsevier
2022-11-01
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| Series: | Arabian Journal of Chemistry |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1878535222005998 |
| _version_ | 1811250727869218816 |
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| author | Ming-Feng Zou Run-Zhu Fan Ai-Ping Yin Rong Hu Dong Huang Wei Li Sheng Yin Rong Pu Gui-Hua Tang |
| author_facet | Ming-Feng Zou Run-Zhu Fan Ai-Ping Yin Rong Hu Dong Huang Wei Li Sheng Yin Rong Pu Gui-Hua Tang |
| author_sort | Ming-Feng Zou |
| collection | DOAJ |
| description | Structural modification of natural products is an effective strategy to discover potent lead compounds with improved medicinal performance. Toosendanin (TSN), a natural limonoid with diverse pharmacological properties, was selected as the starting material for structural modification to obtain more active anti-cancer agents in the current study. A library containing 25 structurally diverse derivatives (including 12 new ones) were constructed on the basis of the structure-guided modification of TSN. Subsequent cytotoxic assay of this library discovered that compounds 14, 18, and 25 showed more significant antiproliferative activity than the precursor TSN in MDA-MB-468 cell model and so as compounds 14, 17–19, 21, and 25 in Hela cell model. Among them, the new derivative 29-O-(6-chloronicotinoyl)-toosendanin (25) exhibited the most potent antiproliferative activity (IC50s 0.05–0.06 μM), being more active than TSN (IC50s 0.14–0.24 μM) and even the first-line drug adriamycin (IC50s ∼ 0.07 μM) in both tested cancer cell lines. The SARs study uncovered that the hemiacetal group, the 14,15-epoxy ring, 1-OH, 7-OH, 3-OAc, and 12-OAc were viewed as the essential active groups and the 29-OH was the critically active modification position of TSN for the enhancement of cytotoxicity. The discovering of 25 from TSN-based derivatives might serve as a lead compound for anti-cancer chemotherapy, which may shed light on rationally design TSN-based derivatives for obtaining more potent anti-tumor agents. |
| first_indexed | 2024-04-12T16:08:58Z |
| format | Article |
| id | doaj.art-6f48945d25f8494d93d037c594ed6a00 |
| institution | Directory Open Access Journal |
| issn | 1878-5352 |
| language | English |
| last_indexed | 2024-04-12T16:08:58Z |
| publishDate | 2022-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Arabian Journal of Chemistry |
| spelling | doaj.art-6f48945d25f8494d93d037c594ed6a002022-12-22T03:25:57ZengElsevierArabian Journal of Chemistry1878-53522022-11-011511104283Discovery of 29-O-acyl-toosendanin-based derivatives as potent anti-cancer agentsMing-Feng Zou0Run-Zhu Fan1Ai-Ping Yin2Rong Hu3Dong Huang4Wei Li5Sheng Yin6Rong Pu7Gui-Hua Tang8School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, ChinaSchool of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, ChinaDepartment of Clinical Laboratory, the Third People's Hospital of Dongguan, Dongguan 523326, ChinaSchool of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, ChinaSchool of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, ChinaSchool of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, ChinaSchool of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, ChinaDepartment of Clinical Laboratory, the Third People's Hospital of Dongguan, Dongguan 523326, China; Corresponding authors.School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China; Corresponding authors.Structural modification of natural products is an effective strategy to discover potent lead compounds with improved medicinal performance. Toosendanin (TSN), a natural limonoid with diverse pharmacological properties, was selected as the starting material for structural modification to obtain more active anti-cancer agents in the current study. A library containing 25 structurally diverse derivatives (including 12 new ones) were constructed on the basis of the structure-guided modification of TSN. Subsequent cytotoxic assay of this library discovered that compounds 14, 18, and 25 showed more significant antiproliferative activity than the precursor TSN in MDA-MB-468 cell model and so as compounds 14, 17–19, 21, and 25 in Hela cell model. Among them, the new derivative 29-O-(6-chloronicotinoyl)-toosendanin (25) exhibited the most potent antiproliferative activity (IC50s 0.05–0.06 μM), being more active than TSN (IC50s 0.14–0.24 μM) and even the first-line drug adriamycin (IC50s ∼ 0.07 μM) in both tested cancer cell lines. The SARs study uncovered that the hemiacetal group, the 14,15-epoxy ring, 1-OH, 7-OH, 3-OAc, and 12-OAc were viewed as the essential active groups and the 29-OH was the critically active modification position of TSN for the enhancement of cytotoxicity. The discovering of 25 from TSN-based derivatives might serve as a lead compound for anti-cancer chemotherapy, which may shed light on rationally design TSN-based derivatives for obtaining more potent anti-tumor agents.http://www.sciencedirect.com/science/article/pii/S1878535222005998Toosendanin derivativesAnti-cancer activityStructure−activity relationships |
| spellingShingle | Ming-Feng Zou Run-Zhu Fan Ai-Ping Yin Rong Hu Dong Huang Wei Li Sheng Yin Rong Pu Gui-Hua Tang Discovery of 29-O-acyl-toosendanin-based derivatives as potent anti-cancer agents Arabian Journal of Chemistry Toosendanin derivatives Anti-cancer activity Structure−activity relationships |
| title | Discovery of 29-O-acyl-toosendanin-based derivatives as potent anti-cancer agents |
| title_full | Discovery of 29-O-acyl-toosendanin-based derivatives as potent anti-cancer agents |
| title_fullStr | Discovery of 29-O-acyl-toosendanin-based derivatives as potent anti-cancer agents |
| title_full_unstemmed | Discovery of 29-O-acyl-toosendanin-based derivatives as potent anti-cancer agents |
| title_short | Discovery of 29-O-acyl-toosendanin-based derivatives as potent anti-cancer agents |
| title_sort | discovery of 29 o acyl toosendanin based derivatives as potent anti cancer agents |
| topic | Toosendanin derivatives Anti-cancer activity Structure−activity relationships |
| url | http://www.sciencedirect.com/science/article/pii/S1878535222005998 |
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