Department of Pharmaceutical Chemistry, School of Pharmacy, International Medical University, Bukit Jalil, 57000 Kuala Lumpur, Malaysia.
Dalton Trans. 2013 Jul 28;42(28):10233-43. doi: 10.1039/c3dt50884f.
Chiral enantiomers [Cu(phen)(L-threo)(H2O)]NO3 1 and [Cu(phen)(D-threo)(H2O)]NO3 2 (threo = threoninate) underwent aldol-type condensation with formaldehyde, with retention of chirality, to yield their respective enantiomeric ternary copper(II) complexes, viz. L- and D-[Cu(phen)(5MeOCA)(H2O)]NO3·xH2O (3 and 4; phen = 1,10-phenanthroline; 5MeOCA = 5-methyloxazolidine-4-carboxylate; x = 0-3) respectively. These chiral complexes were characterized by FTIR, elemental analysis, circular dichroism, UV-Visible spectroscopy, fluorescence spectroscopy (FL), molar conductivity measurement, ESI-MS and X-ray crystallography. Analysis of restriction enzyme inhibition by these four complexes revealed modulation of DNA binding selectivity by the type of ligand, ligand modification and chirality. Their interaction with bovine serum albumin was investigated by FL and electronic spectroscopy. With the aid of the crystal structure of BSA, spectroscopic evidence suggested their binding at the cavity containing Trp134 with numerous Tyr residues in subdomain IA. The products were more antiproliferative than cisplatin against cancer cell lines HK-1, MCF-7, HCT116, HSC-2 and C666-1 except HL-60, and were selective towards nasopharyngeal cancer HK-1 cells over normal NP69 cells of the same organ type.
手性对映异构体 [Cu(phen)(L-threo)(H2O)]NO3 1 和 [Cu(phen)(D-threo)(H2O)]NO3 2（threo = threoninate）与甲醛发生 aldol 型缩合反应，保留了手性，生成各自的对映体三元铜（II）配合物，即 L-和 D-[Cu(phen)(5MeOCA)(H2O)]NO3·xH2O（3 和 4；phen = 1,10-邻菲罗啉；5MeOCA = 5-甲基恶唑烷-4-羧酸酯；x = 0-3）。这些手性配合物通过 FTIR、元素分析、圆二色性、紫外-可见光谱、荧光光谱（FL）、摩尔电导率测量、ESI-MS 和 X 射线晶体学进行了表征。通过这些四种复合物的限制性内切酶抑制分析发现，配体的类型、配体修饰和手性对手性复合物的 DNA 结合选择性有调节作用。通过 FL 和电子光谱研究了它们与牛血清白蛋白的相互作用。结合 BSA 的晶体结构，光谱证据表明它们与包含 Trp134 的空腔结合，其中含有许多 Tyr 残基的 IA 亚域。这些产物对癌症细胞系 HK-1、MCF-7、HCT116、HSC-2 和 C666-1 的增殖抑制作用强于顺铂，对同种器官类型的正常 NP69 细胞具有选择性，除了 HL-60 细胞。
