Synthesis and Structure-Activity Relationship of Salvinal Derivatives as Potent Microtubule Inhibitors

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

doi:10.3390/ijms24076386

Synthesis and Structure-Activity Relationship of Salvinal Derivatives as Potent Microtubule Inhibitors

Int J Mol Sci. 2023 Mar 28;24(7):6386. doi: 10.3390/ijms24076386.

Authors

Chi-I Chang¹, Cheng-Chih Hsieh^{2

3}, Yung-Shung Wein⁴, Ching-Chuan Kuo^{5

6}, Chi-Yen Chang⁷, Jrhau Lung⁸, Jong-Yuh Cherng⁹, Po-Chen Chu¹⁰, Jang-Yang Chang^{5

11

12}, Yueh-Hsiung Kuo^{13

14

15}

Affiliations

¹ Department of Biological Science and Technology, National Pingtung University of Science and Technology, Pingtung 912, Taiwan.
² Department of Pharmacy, Kaohsiung Veterans General Hospital, Kaohsiung 813, Taiwan.
³ School of Pharmacy and Institute of Pharmacy, National Defense Medical Center, Taipei 114, Taiwan.
⁴ Department of Chemistry, National Taiwan University, Taipei 114, Taiwan.
⁵ Institute of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Miaoli 350, Taiwan.
⁶ Graduate Institute of Biomedical Sciences, China Medical University, Taichung 404, Taiwan.
⁷ National Institute of Cancer Research, National Health Research Institutes, Miaoli 350, Taiwan.
⁸ Department of Medical Research and Development, Chiayi Chang Gung Memorial Hospital, Chiayi Branch, Chiayi 613, Taiwan.
⁹ Department of Chemistry and Biochemistry, National Chung Cheng University, Chiayi 613, Taiwan.
¹⁰ Department of Cosmeceutics and Graduate Institute of Cosmeceutic, China Medical University, Taichung 404, Taiwan.
¹¹ Taipei Cancer Center, Taipei Medical University Hospital, Taipei 110, Taiwan.
¹² TMU Research Center of Cancer Translational Medicine, Taipei Medical University, Taipei 110, Taiwan.
¹³ Department of Chinese Pharmaceutical Sciences and Chinese Medicine Resources, College of Pharmacy, China Medical University, Taichung 404, Taiwan.
¹⁴ Department of Biotechnology, Asia University, Taichung 413, Taiwan.
¹⁵ Chinese Medicine Research Center, China Medical University, Taichung 404, Taiwan.

Abstract

Salvinal is a natural lignan isolated from the roots of Salvia mitorrhiza Bunge (Danshen). Previous studies have demonstrated its anti-proliferative activity in both drug-sensitive and -resistant cancer cell lines, with IC₅₀ 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 25 displayed excellent anticancer activity, with IC₅₀ 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 25 showed depolymerization activity in a dose-dependent manner. Our findings indicate that compound 25 is a promising anticancer agent with depolymerization activity that has potential for the management of malignance.

Keywords: Salvia mitorrhiza; anticancer; lignan; microtubule depolymerization; salvinal.

MeSH terms

Antineoplastic Agents* / pharmacology
Cell Line, Tumor
Cell Proliferation
Dose-Response Relationship, Drug
Drug Screening Assays, Antitumor
Humans
Microtubules
Molecular Docking Simulation
Molecular Structure
Structure-Activity Relationship
Tubulin Modulators / pharmacology

Substances

5-(3-hydroxypropyl)-7-methoxy-2-(3'-methoxy-4'-hydroxyphenyl)-3-benzo(b)furancarbaldehyde
Antineoplastic Agents
Tubulin Modulators

Abstract

MeSH terms

Substances

Grants and funding