Synthesis, characterization, and in vitro cytotoxicity of a Kiteplatin-Ibuprofen Pt(IV) prodrug

被引：34

作者：

Curci, Alessandra ^{[1
]}

Denora, Nunzio ^{[2
]}

Iacobazzi, Rosa Maria ^{[3
]}

Ditaranto, Nicoletta ^{[1
]}

Hoeschele, James D. ^{[4
]}

Margiotta, Nicola ^{[1
]}

Natile, Giovanni ^{[1
]}

机构：

[1] Univ Bari Aldo Moro, Dipartimento Chim, Via E Orabona 4, I-70125 Bari, Italy

[2] Univ Bari Aldo Moro, Dipartimento Farm Sci Farmaco, Via E Orabona 4, I-70125 Bari, Italy

[3] Ist Tumori IRCCS Giovanni Paolo II, Viale O Flacco 65, I-70124 Bari, Italy

[4] Eastern Michigan Univ, Dept Chem, Ypsilanti, MI 48197 USA

来源：

INORGANICA CHIMICA ACTA | 2018年 / 472卷

关键词：

Cisplatin; Kiteplatin; cis-1; 4-DACH; Ibuprofen; Pt(IV) drugs; NSAID; Colon cancer; REFRACTORY COLORECTAL-CANCER; COLON-CARCINOMA CELLS; CYCLOOXYGENASE INHIBITORS; CISPLATIN RESISTANCE; COMPLEXES; DELIVERY; INFLAMMATION; DRUG; DNA; REDUCTION;

D O I：

10.1016/j.ica.2017.07.019

中图分类号：

O61 [无机化学];

学科分类号：

070301 ; 081704 ;

摘要：

The Pt(IV) prodrug of kiteplatin, cis-trans-cis-[PtCl2(RS-Ibuprofen-H)(2)(cis-1,4-DACH)], having in the axial positions two molecules of Ibuprofen, has been synthesised, characterized and tested in vitro. The aim was to potentiate the cytotoxic effect of kiteplatin with the anti-inflammatory activity of Ibuprofen. The reduction potential of the conjugate resulted comparable to those of other reported Pt(IV) carboxylate complexes, ensuring in vivo stability in blood during transport and intracellular reduction with release of the active species. The cytotoxic activity of the complex resulted remarkably potentiated reaching nanomolar activity. It is possible that the coordinated Ibuprofen molecules promote the transport and the accumulation of the complex in tumor cells by increasing its lipophilicity. In addition to the increased uptake, Ibuprofen could also exert an anti-inflammatory action mediated by inhibition of the COX enzymes which are overexpressed in tumors. The use of a conjugate with Pt-bound Ibuprofen can ensure similar cellular uptake and biodistribution for both the anti-inflammatory and the cytotoxic drugs in the exact ratio of 2:1. (C) 2017 Elsevier B.V. All rights reserved.

引用

页码：221 / 228

页数：8

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