Synthesis and Structure–Activity Relationship of Salvinal Derivatives as Potent Microtubule Inhibitors
Salvinal is a natural lignan isolated from the roots of <i>Salvia mitorrhiza</i> Bunge (Danshen). Previous studies have demonstrated its anti-proliferative activity in both drug-sensitive and -resistant cancer cell lines, with IC<sub>50</sub> values ranging from 4–17 µM. In t...
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MDPI AG
2023-03-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/7/6386 |
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| author | Chi-I Chang Cheng-Chih Hsieh Yung-Shung Wein Ching-Chuan Kuo Chi-Yen Chang Jrhau Lung Jong-Yuh Cherng Po-Chen Chu Jang-Yang Chang Yueh-Hsiung Kuo |
| author_facet | Chi-I Chang Cheng-Chih Hsieh Yung-Shung Wein Ching-Chuan Kuo Chi-Yen Chang Jrhau Lung Jong-Yuh Cherng Po-Chen Chu Jang-Yang Chang Yueh-Hsiung Kuo |
| author_sort | Chi-I Chang |
| collection | DOAJ |
| description | Salvinal is a natural lignan isolated from the roots of <i>Salvia mitorrhiza</i> Bunge (Danshen). Previous studies have demonstrated its anti-proliferative activity in both drug-sensitive and -resistant cancer cell lines, with IC<sub>50</sub> values ranging from 4–17 µM. In this study, a series of salvinal derivatives was synthesized and evaluated for the structure–activity relationship. Among the twenty-four salvinal derivatives, six compounds showed better anticancer activity than salvinal. Compound <b>25</b> displayed excellent anticancer activity, with IC<sub>50</sub> values of 0.13–0.14 µM against KB, KB-Vin10 (overexpress MDR/Pgp), and KB-7D (overexpress MRP) human carcinoma cell lines. Based on our in vitro microtubule depolymerization assay, compound <b>25</b> showed depolymerization activity in a dose-dependent manner. Our findings indicate that compound <b>25</b> is a promising anticancer agent with depolymerization activity that has potential for the management of malignance. |
| first_indexed | 2024-03-11T05:34:44Z |
| format | Article |
| id | doaj.art-467288e91d924e40a9e0b10ff248ce42 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T05:34:44Z |
| publishDate | 2023-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-467288e91d924e40a9e0b10ff248ce422023-11-17T16:50:22ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-03-01247638610.3390/ijms24076386Synthesis and Structure–Activity Relationship of Salvinal Derivatives as Potent Microtubule InhibitorsChi-I Chang0Cheng-Chih Hsieh1Yung-Shung Wein2Ching-Chuan Kuo3Chi-Yen Chang4Jrhau Lung5Jong-Yuh Cherng6Po-Chen Chu7Jang-Yang Chang8Yueh-Hsiung Kuo9Department of Biological Science and Technology, National Pingtung University of Science and Technology, Pingtung 912, TaiwanDepartment of Pharmacy, Kaohsiung Veterans General Hospital, Kaohsiung 813, TaiwanDepartment of Chemistry, National Taiwan University, Taipei 114, TaiwanInstitute of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Miaoli 350, TaiwanNational Institute of Cancer Research, National Health Research Institutes, Miaoli 350, TaiwanDepartment of Medical Research and Development, Chiayi Chang Gung Memorial Hospital, Chiayi Branch, Chiayi 613, TaiwanDepartment of Chemistry and Biochemistry, National Chung Cheng University, Chiayi 613, TaiwanDepartment of Cosmeceutics and Graduate Institute of Cosmeceutic, China Medical University, Taichung 404, TaiwanInstitute of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Miaoli 350, TaiwanDepartment of Chinese Pharmaceutical Sciences and Chinese Medicine Resources, College of Pharmacy, China Medical University, Taichung 404, TaiwanSalvinal is a natural lignan isolated from the roots of <i>Salvia mitorrhiza</i> Bunge (Danshen). Previous studies have demonstrated its anti-proliferative activity in both drug-sensitive and -resistant cancer cell lines, with IC<sub>50</sub> values ranging from 4–17 µM. In this study, a series of salvinal derivatives was synthesized and evaluated for the structure–activity relationship. Among the twenty-four salvinal derivatives, six compounds showed better anticancer activity than salvinal. Compound <b>25</b> displayed excellent anticancer activity, with IC<sub>50</sub> values of 0.13–0.14 µM against KB, KB-Vin10 (overexpress MDR/Pgp), and KB-7D (overexpress MRP) human carcinoma cell lines. Based on our in vitro microtubule depolymerization assay, compound <b>25</b> showed depolymerization activity in a dose-dependent manner. Our findings indicate that compound <b>25</b> is a promising anticancer agent with depolymerization activity that has potential for the management of malignance.https://www.mdpi.com/1422-0067/24/7/6386salvinallignan<i>Salvia mitorrhiza</i>anticancermicrotubule depolymerization |
| spellingShingle | Chi-I Chang Cheng-Chih Hsieh Yung-Shung Wein Ching-Chuan Kuo Chi-Yen Chang Jrhau Lung Jong-Yuh Cherng Po-Chen Chu Jang-Yang Chang Yueh-Hsiung Kuo Synthesis and Structure–Activity Relationship of Salvinal Derivatives as Potent Microtubule Inhibitors International Journal of Molecular Sciences salvinal lignan <i>Salvia mitorrhiza</i> anticancer microtubule depolymerization |
| title | Synthesis and Structure–Activity Relationship of Salvinal Derivatives as Potent Microtubule Inhibitors |
| title_full | Synthesis and Structure–Activity Relationship of Salvinal Derivatives as Potent Microtubule Inhibitors |
| title_fullStr | Synthesis and Structure–Activity Relationship of Salvinal Derivatives as Potent Microtubule Inhibitors |
| title_full_unstemmed | Synthesis and Structure–Activity Relationship of Salvinal Derivatives as Potent Microtubule Inhibitors |
| title_short | Synthesis and Structure–Activity Relationship of Salvinal Derivatives as Potent Microtubule Inhibitors |
| title_sort | synthesis and structure activity relationship of salvinal derivatives as potent microtubule inhibitors |
| topic | salvinal lignan <i>Salvia mitorrhiza</i> anticancer microtubule depolymerization |
| url | https://www.mdpi.com/1422-0067/24/7/6386 |
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