Łakomska Iwona, Śmiłowicz Dariusz, Jakubowski Mateusz, Sitkowski Jerzy, Wojtczak Andrzej
Faculty of Chemistry, Nicolaus Copernicus University in Toruń, Gagarina 7, 87-100 Toruń, Poland.
Inorganic Chemistry I-Bioinorganic Chemistry, Ruhr-University Bochum, Universitätsstraße 150, 44801 Bochum, Germany.
Materials (Basel). 2020 Nov 24;13(23):5312. doi: 10.3390/ma13235312.
Herein, we present dicarboxylate platinum(II) complexes of the general formula [Pt(mal)(DMSO)(L)] and [Pt(CBDC)(DMSO)(L)], where L is dbtp 5,7-diutyl-1,2,4-triazolo[1,5-]pyrimidine) or ibmtp (7-isobutyl-5-methyl-1,2,4- triazolo[1,5-]pyrimidine), as prospective prodrugs. The platinum(II) complexes were synthesized in a one-pot reaction between -[PtCl(DMSO)], silver malonate or silver cyclobutane-1,1-dicarboxylate and triazolopyrimidines. All platinum(II) compounds were characterized by FT-IR, and H, C, N and Pt NMR; and their square planar geometries with one monodentate N(3)-bonded 5,7-disubstituted-1,2,4-triazolo[1,5-]pyrimidine, one S-bonded molecule of dimethyl sulfoxide and one O,O-chelating malonato (, ) or O,O-chelating cyclobutane-1,1-dicarboxylato (, ) was determined. Additionally, [Pt(CBDC)(dbtp)(DMSO)] () exhibited (i) substantial in vitro cytotoxicity against the lung adenocarcinoma epithelial cell line (A549) (IC = 5.00 µM) and the cisplatin-resistant human ductal breast epithelial tumor cell line (T47D) (IC = 6.60 µM); and (ii) definitely exhibited low toxicity against normal murine embryonic fibroblast cells (BALB/3T3).
在此，我们展示了通式为[Pt(mal)(DMSO)(L)]和[Pt(CBDC)(DMSO)(L)]的二羧酸铂(II)配合物，其中L为dbtp（5,7-二丁基-1,2,4-三唑并[1,5-a]嘧啶）或ibmtp（7-异丁基-5-甲基-1,2,4-三唑并[1,5-a]嘧啶），作为潜在的前药。铂(II)配合物是通过-[PtCl(DMSO)]、丙二酸银或环丁烷-1,1-二羧酸银与三唑并嘧啶在一锅反应中合成的。所有铂(II)化合物均通过傅里叶变换红外光谱、氢、碳、氮和铂核磁共振进行了表征；并确定了它们的平面正方形几何结构，其中有一个单齿N(3)-键合的5,7-二取代-1,2,4-三唑并[1,5-a]嘧啶、一个S-键合的二甲基亚砜分子和一个O,O-螯合的丙二酸根（, ）或O,O-螯合的环丁烷-1,1-二羧酸根（, ）。此外，[Pt(CBDC)(dbtp)(DMSO)]（）表现出：(i) 对肺腺癌上皮细胞系（A549）（IC = 5.00 μM）和顺铂耐药的人乳腺导管上皮肿瘤细胞系（T47D）（IC = 6.60 μM）具有显著的体外细胞毒性；以及 (ii) 对正常小鼠胚胎成纤维细胞（BALB/3T3）表现出低毒性。
