<i>Cis,cis,trans</i>-[Pt^IVCl₂(NH₃)₂(perillato)₂], a dual-action prodrug with excellent cytotoxic and antimetastatic activity

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-[Pt^IVCl₂(NH₃)₂(perillato)₂] 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.