TY - JOUR
T1 - Antitumor platinum(IV) derivatives of carboplatin and the histone deacetylase inhibitor 4-phenylbutyric acid
AU - Almotairy, Awatif Rashed Z.
AU - Gandin, Valentina
AU - Morrison, Liam
AU - Marzano, Cristina
AU - Montagner, Diego
AU - Erxleben, Andrea
N1 - Publisher Copyright:
© 2017 Elsevier Inc.
PY - 2017/12
Y1 - 2017/12
N2 - 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.
AB - 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.
KW - 4-Phenylbutyric acid
KW - Anticancer
KW - Carboplatin
KW - Histone deacetylase inhibitor
KW - Platinum(IV)
UR - https://www.scopus.com/pages/publications/85029505415
U2 - 10.1016/j.jinorgbio.2017.09.009
DO - 10.1016/j.jinorgbio.2017.09.009
M3 - Article
SN - 0162-0134
VL - 177
SP - 1
EP - 7
JO - Journal of Inorganic Biochemistry
JF - Journal of Inorganic Biochemistry
ER -
