Design, synthesis and biological evaluation of isoxazole-naphthalene derivatives as anti-tubulin agents
In this study, a novel series of isoxazole-naphthalene derivatives as tubulin polymerization inhibitors were designed, synthesized and evaluated for their anti-proliferative activities against human breast cancer cell line MCF-7. Most of the synthesized compounds exhibited moderate to potent antipro...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2020-06-01
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| Series: | Arabian Journal of Chemistry |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1878535220301209 |
| _version_ | 1819066124123242496 |
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| author | Guangcheng Wang Wenjing Liu Yong Huang Yongjun Li Zhiyun Peng |
| author_facet | Guangcheng Wang Wenjing Liu Yong Huang Yongjun Li Zhiyun Peng |
| author_sort | Guangcheng Wang |
| collection | DOAJ |
| description | In this study, a novel series of isoxazole-naphthalene derivatives as tubulin polymerization inhibitors were designed, synthesized and evaluated for their anti-proliferative activities against human breast cancer cell line MCF-7. Most of the synthesized compounds exhibited moderate to potent antiproliferative activity (IC50 < 10.0 μM), as compared to cisplatin (15.24 ± 1.27 μM). Among them, compound 5j containing 4-ethoxy substitution at phenyl ring was found to be the most active compound with IC50 value of 1.23 ± 0.16 μM. Mechanistic studies revealed that compound 5j arrested cell cycle at G2/M phase and induces apoptosis. Furthermore, in vitro tubulin polymerization assay showed that compound 5j displayed better inhibition activity on tubulin polymerization (IC50 = 3.4 μM) than colchicine (IC50 = 7.5 μM). Molecular docking study also revealed that compound 5j binds to the colchicine binding site of tubulin. |
| first_indexed | 2024-12-21T15:57:22Z |
| format | Article |
| id | doaj.art-b8a0398aad4d4aec824c4af114aa0289 |
| institution | Directory Open Access Journal |
| issn | 1878-5352 |
| language | English |
| last_indexed | 2024-12-21T15:57:22Z |
| publishDate | 2020-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Arabian Journal of Chemistry |
| spelling | doaj.art-b8a0398aad4d4aec824c4af114aa02892022-12-21T18:58:03ZengElsevierArabian Journal of Chemistry1878-53522020-06-0113657655775Design, synthesis and biological evaluation of isoxazole-naphthalene derivatives as anti-tubulin agentsGuangcheng Wang0Wenjing Liu1Yong Huang2Yongjun Li3Zhiyun Peng4State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Provincial Key Laboratory of Pharmaceutics, Guizhou Medical University, Guiyang, China; College of Chemistry and Chemical Engineering, Jishou University, Jishou, China; Corresponding authors at: State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Provincial Key Laboratory of Pharmaceutics, Guizhou Medical University, Guiyang, China (G. Wang); College of Food Science and Technology, Shanghai Ocean University, Shanghai, China (Z. Peng).State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Provincial Key Laboratory of Pharmaceutics, Guizhou Medical University, Guiyang, China; Engineering Research Center for the Development and Application of Ethnic Medicine and TCM (Ministry of Education), Guizhou Medical University, Guiyang, China; School of Pharmacy, Guizhou Medical University, Guiyang, ChinaState Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Provincial Key Laboratory of Pharmaceutics, Guizhou Medical University, Guiyang, ChinaEngineering Research Center for the Development and Application of Ethnic Medicine and TCM (Ministry of Education), Guizhou Medical University, Guiyang, ChinaCollege of Food Science and Technology, Shanghai Ocean University, Shanghai, China; Corresponding authors at: State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Provincial Key Laboratory of Pharmaceutics, Guizhou Medical University, Guiyang, China (G. Wang); College of Food Science and Technology, Shanghai Ocean University, Shanghai, China (Z. Peng).In this study, a novel series of isoxazole-naphthalene derivatives as tubulin polymerization inhibitors were designed, synthesized and evaluated for their anti-proliferative activities against human breast cancer cell line MCF-7. Most of the synthesized compounds exhibited moderate to potent antiproliferative activity (IC50 < 10.0 μM), as compared to cisplatin (15.24 ± 1.27 μM). Among them, compound 5j containing 4-ethoxy substitution at phenyl ring was found to be the most active compound with IC50 value of 1.23 ± 0.16 μM. Mechanistic studies revealed that compound 5j arrested cell cycle at G2/M phase and induces apoptosis. Furthermore, in vitro tubulin polymerization assay showed that compound 5j displayed better inhibition activity on tubulin polymerization (IC50 = 3.4 μM) than colchicine (IC50 = 7.5 μM). Molecular docking study also revealed that compound 5j binds to the colchicine binding site of tubulin.http://www.sciencedirect.com/science/article/pii/S1878535220301209IsoxazoleNaphthaleneAnti-tubulin agentsTubulin polymerizationAntitumor |
| spellingShingle | Guangcheng Wang Wenjing Liu Yong Huang Yongjun Li Zhiyun Peng Design, synthesis and biological evaluation of isoxazole-naphthalene derivatives as anti-tubulin agents Arabian Journal of Chemistry Isoxazole Naphthalene Anti-tubulin agents Tubulin polymerization Antitumor |
| title | Design, synthesis and biological evaluation of isoxazole-naphthalene derivatives as anti-tubulin agents |
| title_full | Design, synthesis and biological evaluation of isoxazole-naphthalene derivatives as anti-tubulin agents |
| title_fullStr | Design, synthesis and biological evaluation of isoxazole-naphthalene derivatives as anti-tubulin agents |
| title_full_unstemmed | Design, synthesis and biological evaluation of isoxazole-naphthalene derivatives as anti-tubulin agents |
| title_short | Design, synthesis and biological evaluation of isoxazole-naphthalene derivatives as anti-tubulin agents |
| title_sort | design synthesis and biological evaluation of isoxazole naphthalene derivatives as anti tubulin agents |
| topic | Isoxazole Naphthalene Anti-tubulin agents Tubulin polymerization Antitumor |
| url | http://www.sciencedirect.com/science/article/pii/S1878535220301209 |
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