Design, synthesis and antitumor activity of 3,4,5-Trisubstituted Isoxazoles

In this study, 56 isoxazole derivatives were synthesized and their antitumor activity against 9 cancer cells, such as BXPC-3, MiaPaCa-2, PANC-1, MCF-7, HCT-116, HepG2, NCI-H460, A549 and B16 was detected. The results of pharmacological experiments indicated that most compounds exhibit good cytotoxic...

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Main Authors: Kanghui Duan, Fuxing Tan, Hongming Xie, Haiwang Liu, Yingjun Zhang, Huanfeng Jiang, Wanqing Wu
Format: Article
Language:English
Published: Elsevier 2024-12-01
Series:European Journal of Medicinal Chemistry Reports
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Online Access:http://www.sciencedirect.com/science/article/pii/S277241742400075X
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author Kanghui Duan
Fuxing Tan
Hongming Xie
Haiwang Liu
Yingjun Zhang
Huanfeng Jiang
Wanqing Wu
author_facet Kanghui Duan
Fuxing Tan
Hongming Xie
Haiwang Liu
Yingjun Zhang
Huanfeng Jiang
Wanqing Wu
author_sort Kanghui Duan
collection DOAJ
description In this study, 56 isoxazole derivatives were synthesized and their antitumor activity against 9 cancer cells, such as BXPC-3, MiaPaCa-2, PANC-1, MCF-7, HCT-116, HepG2, NCI-H460, A549 and B16 was detected. The results of pharmacological experiments indicated that most compounds exhibit good cytotoxicity against nine cancer cells. Among them, compound 14–3 has an IC50 of 2.4 μM for colon cancer cells HCT-116, which shows the best effect and is better than the broad-spectrum drug 5-Fluorouracil (5-Fu) for the treatment of colon cancer. In addition, 14–3 induces apoptosis and leads to cell cycle arrest in the G2/M phase. Cytotoxicity tests on human normal hepatocytes LO2 also demonstrates that 14–3 is less toxic than 5-Fu with no obvious toxicity. These results suggest that 14–3 is a potential candidate for the development of anti-tumor drugs.
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institution Kabale University
issn 2772-4174
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publishDate 2024-12-01
publisher Elsevier
record_format Article
series European Journal of Medicinal Chemistry Reports
spelling doaj-art-0adbbff9568d40c1bbc1e9fffb5099eb2024-12-05T05:21:53ZengElsevierEuropean Journal of Medicinal Chemistry Reports2772-41742024-12-0112100203Design, synthesis and antitumor activity of 3,4,5-Trisubstituted IsoxazolesKanghui Duan0Fuxing Tan1Hongming Xie2Haiwang Liu3Yingjun Zhang4Huanfeng Jiang5Wanqing Wu6Key Laboratory of Functional Molecular Engineering of Guangdong Province, School of Chemistry and Chemical Engineering, South China University of Technology, Guangzhou, 510640, ChinaState Key Laboratory of Anti-Infective Drug Development, Sunshine Lake Pharma Company, Ltd., Dongguan, 523871, ChinaState Key Laboratory of Anti-Infective Drug Development, Sunshine Lake Pharma Company, Ltd., Dongguan, 523871, ChinaState Key Laboratory of Anti-Infective Drug Development, Sunshine Lake Pharma Company, Ltd., Dongguan, 523871, ChinaState Key Laboratory of Anti-Infective Drug Development, Sunshine Lake Pharma Company, Ltd., Dongguan, 523871, ChinaKey Laboratory of Functional Molecular Engineering of Guangdong Province, School of Chemistry and Chemical Engineering, South China University of Technology, Guangzhou, 510640, ChinaKey Laboratory of Functional Molecular Engineering of Guangdong Province, School of Chemistry and Chemical Engineering, South China University of Technology, Guangzhou, 510640, China; Corresponding author.In this study, 56 isoxazole derivatives were synthesized and their antitumor activity against 9 cancer cells, such as BXPC-3, MiaPaCa-2, PANC-1, MCF-7, HCT-116, HepG2, NCI-H460, A549 and B16 was detected. The results of pharmacological experiments indicated that most compounds exhibit good cytotoxicity against nine cancer cells. Among them, compound 14–3 has an IC50 of 2.4 μM for colon cancer cells HCT-116, which shows the best effect and is better than the broad-spectrum drug 5-Fluorouracil (5-Fu) for the treatment of colon cancer. In addition, 14–3 induces apoptosis and leads to cell cycle arrest in the G2/M phase. Cytotoxicity tests on human normal hepatocytes LO2 also demonstrates that 14–3 is less toxic than 5-Fu with no obvious toxicity. These results suggest that 14–3 is a potential candidate for the development of anti-tumor drugs.http://www.sciencedirect.com/science/article/pii/S277241742400075XIsoxazoleHCT-1165-FluorouracilAnti-tumor
spellingShingle Kanghui Duan
Fuxing Tan
Hongming Xie
Haiwang Liu
Yingjun Zhang
Huanfeng Jiang
Wanqing Wu
Design, synthesis and antitumor activity of 3,4,5-Trisubstituted Isoxazoles
European Journal of Medicinal Chemistry Reports
Isoxazole
HCT-116
5-Fluorouracil
Anti-tumor
title Design, synthesis and antitumor activity of 3,4,5-Trisubstituted Isoxazoles
title_full Design, synthesis and antitumor activity of 3,4,5-Trisubstituted Isoxazoles
title_fullStr Design, synthesis and antitumor activity of 3,4,5-Trisubstituted Isoxazoles
title_full_unstemmed Design, synthesis and antitumor activity of 3,4,5-Trisubstituted Isoxazoles
title_short Design, synthesis and antitumor activity of 3,4,5-Trisubstituted Isoxazoles
title_sort design synthesis and antitumor activity of 3 4 5 trisubstituted isoxazoles
topic Isoxazole
HCT-116
5-Fluorouracil
Anti-tumor
url http://www.sciencedirect.com/science/article/pii/S277241742400075X
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AT haiwangliu designsynthesisandantitumoractivityof345trisubstitutedisoxazoles
AT yingjunzhang designsynthesisandantitumoractivityof345trisubstitutedisoxazoles
AT huanfengjiang designsynthesisandantitumoractivityof345trisubstitutedisoxazoles
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