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沙蟾毒精衍生物的合成及构效关系研究作为有效的微管抑制剂。

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

机构信息

Department of Biological Science and Technology, National Pingtung University of Science and Technology, Pingtung 912, Taiwan.

Department of Pharmacy, Kaohsiung Veterans General Hospital, Kaohsiung 813, Taiwan.

出版信息

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

DOI:10.3390/ijms24076386
PMID:37047358
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10093915/
Abstract

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

摘要

salvinal 是从丹参的根部分离得到的天然木脂素。先前的研究表明，它对敏感和耐药的癌细胞系均具有抗增殖活性，IC 值范围为 4-17µM。在本研究中，合成了一系列 salvinal 衍生物，并对其进行了构效关系评价。在所合成的 24 个 salvinal 衍生物中，有 6 个化合物的抗癌活性优于 salvinal。化合物 显示出优异的抗癌活性，对 KB、KB-Vin10（过表达 MDR/Pgp）和 KB-7D（过表达 MRP）人癌细胞系的 IC 值分别为 0.13-0.14µM。基于我们的体外微管解聚实验，化合物 表现出剂量依赖性的解聚活性。我们的研究结果表明，化合物 是一种具有解聚活性的有前途的抗癌药物，有望用于恶性肿瘤的治疗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cf82/10093915/0173c1abbba7/ijms-24-06386-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cf82/10093915/0ef1fb8dfe57/ijms-24-06386-sch001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cf82/10093915/05c830bacf25/ijms-24-06386-sch002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cf82/10093915/e4014b4bb69d/ijms-24-06386-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cf82/10093915/0173c1abbba7/ijms-24-06386-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cf82/10093915/0ef1fb8dfe57/ijms-24-06386-sch001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cf82/10093915/05c830bacf25/ijms-24-06386-sch002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cf82/10093915/e4014b4bb69d/ijms-24-06386-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cf82/10093915/0173c1abbba7/ijms-24-06386-g002.jpg

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