Cyclopalladated Benzophenone Imines: Synthesis, Antitumor Activity, Cell Accumulation, DNA Interaction, and Cathepsin B Inhibition
Cyclopalladated Benzophenone Imines: Synthesis, Antitumor Activity, Cell Accumulation, DNA Interaction, and Cathepsin B Inhibition
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DOI：
10.1021/om501060f
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发表时间：
2014-12
期刊：
影响因子：
2.8
通讯作者：
J. Albert;J. Granell;Romana Qadir;J. Quirante;C. Calvis;R. Messeguer;J. Badía;L. Baldomá;M. Font‐B
中科院分区：
文献类型：
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作者：
J. Albert;J. Granell;Romana Qadir;J. Quirante;C. Calvis;R. Messeguer;J. Badía;L. Baldomá;M. Font‐B
5元环邻苯二苯甲酮亚胺[Pd{C6H4(Ph)C═NR}]2(μ-X)2[1(X=OAc)，2(X=Cl)，a(R=苯基)，b(R=1-萘基)，c(R=苯基)，d(R=α-甲基苯基)]和反式N，P-[Pd{C6H4(Ph)C═NR}X(PPh3)][3(X=OAc)，4(X=Cl)，a(R=苯基)]和反式N，P-[Pd{C6H4(Ph)C═NR}X(PPh3)]的合成B(R=1-萘基)，c(R=苄基)，d(R=α-甲基苄基)]和1a，1c，1d，4a，4b和4c的X射线分子结构。研究了钯化合物a-d的抗肿瘤活性、DNA相互作用和对组织蛋白酶B的抑制作用，并与已报道的具有R=H的钯化合物e和类似于4e但以铂(II)为中心的化合物4f的抗肿瘤活性进行了比较。针对一组人类癌细胞株的IC50值允许在它们的结构和抗肿瘤活性之间建立定性的关系。化合物3E、4E和4F的体外抗癌活性最强。化合物3E和4E的活性约为顺铂的4倍。
The synthesis of the endo five-membered cyclo-ortho-palladated benzophenone imines [Pd{C6H4(Ph)C═NR}]2(μ-X)2 [1 (X = OAc), 2 (X = Cl), a (R = phenyl), b (R = 1-naphthyl), c (R = benzyl), d (R = α-methylbenzyl)], and trans-N,P-[Pd{C6H4(Ph)C═NR}X(PPh3)] [3 (X = OAc), 4 (X = Cl), a (R = phenyl), b (R = 1-naphthyl), c (R = benzyl), d (R = α-methylbenzyl)] and the X-ray molecular structure of 1a, 1c, 1d, 4a, 4b, and 4c are reported. The antitumor activity, DNA interaction, and cathepsin B inhibition of palladium compounds a–d were studied and compared with those previously reported for palladium compounds e with R = H and compound 4f analogous to 4e but with a platinum(II) center. The IC50 values against a panel of human cancer cell lines allowed the establishment of a qualitative relationship between their structure and antitumor activity. Compounds 3e, 4e, and 4f were the most active ones in relation to their in vitro anticancer activity. Compounds 3e and 4e were about 4 times more active than cisplatin agai...