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
Almotairy, Awatif Rashed Z.
Gandin, Valentina
Morrison, Liam
Marzano, Cristina
Montagner, Diego
Erxleben, Andrea
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Publication Date
2017-09-10
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Article
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Almotairy, Awatif Rashed Z., Gandin, Valentina, Morrison, Liam, Marzano, Cristina, Montagner, Diego, & Erxleben, Andrea. (2017). Antitumor platinum(IV) derivatives of carboplatin and the histone deacetylase inhibitor 4-phenylbutyric acid. Journal of Inorganic Biochemistry, 177, 1-7. doi: https://doi.org/10.1016/j.jinorgbio.2017.09.009
Abstract
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.
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Publisher
Elsevier
Publisher DOI
10.1016/j.jinorgbio.2017.09.009
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Attribution-NonCommercial-NoDerivs 3.0 Ireland