Synthesis, in‐vitro cytotoxic activity and DNA interactions of new dicarboxylatoplatinum(II) complexes with 2‐hydroxymethylbenzimidazole as carrier ligands. (11th August 2014)

• Record Type: Journal Article
• Authors: Utku, Semra; Özçelik, Azime Berna; Gümüş, Fatma; Yılmaz, Şükran; Arsoy, Taibe; Açık, Leyla; Çelebi Keskin, Ayten
• Is Part Of: Journal of pharmacy and pharmacology. Volume 66:Number 11(2014:Nov.)
• Page Start: 1593
• Page End: 1605
• Publication Date: 2014-08-11
• Subjects: Pharmacy -- Periodicals; Pharmacology -- Periodicals; 615.1
• DOI: 10.1111/jphp.12290
• Languages: English
• ISSNs: 0022-3573

Abstract

<abstract abstract-type="main"> <title>Abstract</title> <sec id="jphp12290-sec-0001" sec-type="section"> <title>Objectives</title> <p>The aim of this study was to investigate the in‐vitro cytotoxic activity of new platinum(II) complexes on the human HeLa (ER−), MCF‐7 (ER+) and MDA‐MB 231 (ER−) cell lines. Furthermore, we investigated plasmid DNA interactions and inhibition of <italic>Bam</italic>HI and <italic>Hind</italic>III restriction enzyme activity of the complex <bold>1</bold>–<bold>4</bold>, <bold>7</bold>.</p> </sec> <sec id="jphp12290-sec-0002" sec-type="section"> <title>Methods</title> <p>Platinum(II) complexes were synthesised from precursor complexes of [PtL<sub>2</sub>Cl<sub>2</sub>] and [PtL<sub>2</sub>I<sub>2</sub>]. Their cytotoxic activity was tested by MTT (3‐(4, 5‐dimethylthiazol‐2‐yl)‐2, 5‐diphenyltetrazolium bromide) assay. Their plasmid DNA interactions and restriction enzyme activities were also investigated using the agarose gel electrophoresis method.</p> </sec> <sec id="jphp12290-sec-0003" sec-type="section"> <title>Key findings</title> <p>The growth inhibitory effect results showed that the cytotoxicity of complex <bold>2</bold> was found to be the most active complex among the synthesised complexes.</p> </sec> <sec id="jphp12290-sec-0004" sec-type="section"> <title>Conclusions</title> <p>The MTT results showed that complex <bold>2</bold> was found to be cytotoxic equal to cisplatin and higher than carboplatin against the MCF‐7 and MDA‐MB‐231 cell lines. Furthermore, the estrogen or progesterone co‐treatment slightly increased the cytotoxicity of complex <bold>2</bold>, the cisplatin and carboplatin compared with the complex <bold>2</bold> tested alone in 50 μ<sc>m</sc> concentration. According to plasmid DNA interaction and the restriction studies, complexes <bold>1</bold>–<bold>4, 7</bold> modified the tertiary structure of pBR322 plasmid DNA, and complexes <bold>2–4</bold> prevented enzyme digestion at high concentrations.</p> </sec> </abstract>