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Antitumor platinum(IV) derivatives of carboplatin and the histone deacetylase inhibitor 4-phenylbutyric acid
Almotairy, Awatif Rashed Z.; Gandin, Valentina; Morrison, Liam; Marzano, Cristina; Montagner, Diego; Erxleben, Andrea
Five new platinum(IV) derivatives of carboplatin each incorporating the histone deacetylase inhibitor 4-phenylbutyrate in axial position were synthesized and characterized by 1H and 195Pt NMR spectroscopy, electrospray ionization mass spectrometry and elemental analysis, namely cis,trans-[Pt(CBDCA)(NH3)2(PBA)(OH)] (1), cis,trans-[Pt(CBDCA)(NH3)2(PBA)2] (2), cis,trans-[Pt(CBDCA)(NH3)2(PBA)(bz)] (3), cis,trans-[Pt(CBDCA)(NH3)2(PBA)(suc)] (4) and cis,trans-[Pt(CBDCA)(NH3)2)(PBA)(ac)] (5) (PBA = 4-phenylbutyrate, CBDCA = 1,1-cyclobutane dicarboxylate, bz = benzoate, suc = succinate and ac = acetate). The reduction behavior in the presence of ascorbic acid was studied by high performance liquid chromatography. The cytotoxicity against a panel of human tumor cell lines, histone deacetylase (HDAC) inhibitory activity, cellular accumulation and the ability to induce apoptosis were evaluated. The most effective complex, compound 3, was found to be up to ten times more effective than carboplatin and to decrease cellular basal HDAC activity by approximately 18% in A431 human cervical cancer cells. A.A. acknowledges the Royal Embassy of Saudi Arabia Ministry of Education for a Saudi Arabia Government Scholarship. V.G. and C.M. acknowledge the University of Padova (grants 60A04-0443, 60A04-3189 and 60A04-4015/15, DOR2016). 2019-09-10
Keyword(s): Anticancer; Carboplatin; Histone deacetylase inhibitor; 4-Phenylbutyric acid; Platinum(IV)
Publication Date:
2018
Type: Journal article
Peer-Reviewed: Yes
Language(s): English
Institution: NUI Galway
Publisher(s): Elsevier
File Format(s): application/pdf
First Indexed: 2018-03-15 06:21:40 Last Updated: 2018-03-15 06:21:40