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顺式,顺式,反式-[PtCl(NH)(川芎嗪)], 一种具有优异细胞毒性和抗转移活性的双重作用前药。

Cis,cis,trans-[PtCl(NH)(perillato)], a dual-action prodrug with excellent cytotoxic and antimetastatic activity.

机构信息

Dipartimento di Scienze e Innovazione Tecnologica, Università del Piemonte Orientale, Viale Michel 11, 15121 Alessandria, Italy.

出版信息

Dalton Trans. 2021 Mar 7;50(9):3161-3177. doi: 10.1039/d0dt04051g. Epub 2021 Feb 17.

DOI:10.1039/d0dt04051g
PMID:33595015
Abstract

Two Pt(iv) conjugates containing one or two molecules of perillic acid (4-isopropenylcyclohexene-1-carboxylic acid), an active metabolite of limonene, were synthesized both with traditional and microwave-assisted methods and characterized. Their antiproliferative activity was tested on a panel of human tumor cell lines. In particular, cis,cis,trans-[PtCl(NH)(perillato)] exhibited excellent antiproliferative and antimetastatic activity on A-549 lung tumor cells at nanomolar concentrations. A number of in vitro biological tests were performed to decipher some aspects of its mechanism of action, including transwell migration and invasion as well as wound healing assay.

摘要

合成了两种含有一个或两个薄荷酸(4-异丙烯基环己烯-1-羧酸)分子的 Pt(iv) 配合物,薄荷酸是柠檬烯的一种活性代谢物,分别采用传统方法和微波辅助方法进行了合成和表征。它们的抗增殖活性在一组人类肿瘤细胞系上进行了测试。特别是顺式、顺式、反式-[PtCl(NH)(perillato)]在纳摩尔浓度下对 A-549 肺肿瘤细胞表现出优异的抗增殖和抗转移活性。进行了多项体外生物学测试来阐明其作用机制的一些方面,包括 Transwell 迁移和侵袭以及伤口愈合测定。

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