Design, synthesis, and evaluation of cyclic C7-bridged monocarbonyl curcumin analogs containing an o-methoxy phenyl group as potential agents against gastric cancer
The structure-activity relationship (SAR) between toxicity and the types of linking ketones of C7 bridged monocarbonyl curcumin analogs (MCAs) was not clear yet. In the pursuit of effective and less cytotoxic chemotherapeutics, we conducted a SAR analysis using various diketene skeletons of C7-bridg...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2024-12-01
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| Series: | Journal of Enzyme Inhibition and Medicinal Chemistry |
| Subjects: | |
| Online Access: | https://www.tandfonline.com/doi/10.1080/14756366.2024.2314233 |
| _version_ | 1826919922057347072 |
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| author | Xin Gan Yuna Wu Min Zhu Bo Liu Miaomiao Kong Zixuan Xi Ke Li Haibao Wang Tiande Su Jiali Yao Fatehi Khushafah Baozhu Yi Jiabing Wang Wulan Li Jianzhang Wu |
| author_facet | Xin Gan Yuna Wu Min Zhu Bo Liu Miaomiao Kong Zixuan Xi Ke Li Haibao Wang Tiande Su Jiali Yao Fatehi Khushafah Baozhu Yi Jiabing Wang Wulan Li Jianzhang Wu |
| author_sort | Xin Gan |
| collection | DOAJ |
| description | The structure-activity relationship (SAR) between toxicity and the types of linking ketones of C7 bridged monocarbonyl curcumin analogs (MCAs) was not clear yet. In the pursuit of effective and less cytotoxic chemotherapeutics, we conducted a SAR analysis using various diketene skeletons of C7-bridged MCAs, synthesized cyclic C7-bridged MCAs containing the identified low-toxicity cyclopentanone scaffold and an o-methoxy phenyl group, and assessed their anti-gastric cancer activity and safety profile. Most compounds exhibited potent cytotoxic activities against gastric cancer cells. We developed a quantitative structure-activity relationship model (R2 > 0.82) by random Forest method, providing important information for optimizing structure. An optimized compound 2 exhibited in vitro and in vivo anti-gastric cancer activity partly through inhibiting the AKT and STAT3 pathways, and displayed a favorable in vivo safety profile. In summary, this paper provided a promising class of MCAs and a potential compound for the development of chemotherapeutic drugs. |
| first_indexed | 2024-03-07T23:02:30Z |
| format | Article |
| id | doaj.art-cb72a492c29b4ee6b5e53c1edd2e3bc8 |
| institution | Directory Open Access Journal |
| issn | 1475-6366 1475-6374 |
| language | English |
| last_indexed | 2025-02-17T13:20:35Z |
| publishDate | 2024-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Journal of Enzyme Inhibition and Medicinal Chemistry |
| spelling | doaj.art-cb72a492c29b4ee6b5e53c1edd2e3bc82024-12-26T09:30:44ZengTaylor & Francis GroupJournal of Enzyme Inhibition and Medicinal Chemistry1475-63661475-63742024-12-0139110.1080/14756366.2024.2314233Design, synthesis, and evaluation of cyclic C7-bridged monocarbonyl curcumin analogs containing an o-methoxy phenyl group as potential agents against gastric cancerXin Gan0Yuna Wu1Min Zhu2Bo Liu3Miaomiao Kong4Zixuan Xi5Ke Li6Haibao Wang7Tiande Su8Jiali Yao9Fatehi Khushafah10Baozhu Yi11Jiabing Wang12Wulan Li13Jianzhang Wu14The Second Affiliated Hospital and Yuying Children’s Hospital of the Wenzhou Medical University, Wenzhou, ChinaThe Eye Hospital, School of Ophthalmology & Optometry, Wenzhou Medical University, Wenzhou, ChinaSchool of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, ChinaThe First Affiliated Hospital of Wenzhou Medical University, Wenzhou, ChinaThe First Affiliated Hospital of Wenzhou Medical University, Wenzhou, ChinaThe First Affiliated Hospital of Wenzhou Medical University, Wenzhou, ChinaThe First Affiliated Hospital of Wenzhou Medical University, Wenzhou, ChinaMunicipal Hospital Affiliated to Taizhou University, Taizhou, ChinaSchool of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, ChinaSchool of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, ChinaSchool of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, ChinaThe Second Affiliated Hospital and Yuying Children’s Hospital of the Wenzhou Medical University, Wenzhou, ChinaMunicipal Hospital Affiliated to Taizhou University, Taizhou, ChinaThe First Affiliated Hospital of Wenzhou Medical University, Wenzhou, ChinaThe Second Affiliated Hospital and Yuying Children’s Hospital of the Wenzhou Medical University, Wenzhou, ChinaThe structure-activity relationship (SAR) between toxicity and the types of linking ketones of C7 bridged monocarbonyl curcumin analogs (MCAs) was not clear yet. In the pursuit of effective and less cytotoxic chemotherapeutics, we conducted a SAR analysis using various diketene skeletons of C7-bridged MCAs, synthesized cyclic C7-bridged MCAs containing the identified low-toxicity cyclopentanone scaffold and an o-methoxy phenyl group, and assessed their anti-gastric cancer activity and safety profile. Most compounds exhibited potent cytotoxic activities against gastric cancer cells. We developed a quantitative structure-activity relationship model (R2 > 0.82) by random Forest method, providing important information for optimizing structure. An optimized compound 2 exhibited in vitro and in vivo anti-gastric cancer activity partly through inhibiting the AKT and STAT3 pathways, and displayed a favorable in vivo safety profile. In summary, this paper provided a promising class of MCAs and a potential compound for the development of chemotherapeutic drugs.https://www.tandfonline.com/doi/10.1080/14756366.2024.2314233Cyclic C7 bridged monocarbonyl curcumin analoguessynthesisanticancer activityQSAR based on artificial intelligenceAKT/STAT3 inhibitor |
| spellingShingle | Xin Gan Yuna Wu Min Zhu Bo Liu Miaomiao Kong Zixuan Xi Ke Li Haibao Wang Tiande Su Jiali Yao Fatehi Khushafah Baozhu Yi Jiabing Wang Wulan Li Jianzhang Wu Design, synthesis, and evaluation of cyclic C7-bridged monocarbonyl curcumin analogs containing an o-methoxy phenyl group as potential agents against gastric cancer Journal of Enzyme Inhibition and Medicinal Chemistry Cyclic C7 bridged monocarbonyl curcumin analogues synthesis anticancer activity QSAR based on artificial intelligence AKT/STAT3 inhibitor |
| title | Design, synthesis, and evaluation of cyclic C7-bridged monocarbonyl curcumin analogs containing an o-methoxy phenyl group as potential agents against gastric cancer |
| title_full | Design, synthesis, and evaluation of cyclic C7-bridged monocarbonyl curcumin analogs containing an o-methoxy phenyl group as potential agents against gastric cancer |
| title_fullStr | Design, synthesis, and evaluation of cyclic C7-bridged monocarbonyl curcumin analogs containing an o-methoxy phenyl group as potential agents against gastric cancer |
| title_full_unstemmed | Design, synthesis, and evaluation of cyclic C7-bridged monocarbonyl curcumin analogs containing an o-methoxy phenyl group as potential agents against gastric cancer |
| title_short | Design, synthesis, and evaluation of cyclic C7-bridged monocarbonyl curcumin analogs containing an o-methoxy phenyl group as potential agents against gastric cancer |
| title_sort | design synthesis and evaluation of cyclic c7 bridged monocarbonyl curcumin analogs containing an o methoxy phenyl group as potential agents against gastric cancer |
| topic | Cyclic C7 bridged monocarbonyl curcumin analogues synthesis anticancer activity QSAR based on artificial intelligence AKT/STAT3 inhibitor |
| url | https://www.tandfonline.com/doi/10.1080/14756366.2024.2314233 |
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