Pharmaceutical Research Center and School of Chemistry and Chemical Engineering, Southeast University, Nanjing 211189, China.
Pharmaceutical Research Center and School of Chemistry and Chemical Engineering, Southeast University, Nanjing 211189, China; Jiangsu Province Hi-Tech Key Laboratory for Bio-medical Research, Southeast University, Nanjing 211189, China.
Eur J Med Chem. 2016 May 23;114:141-52. doi: 10.1016/j.ejmech.2016.02.060. Epub 2016 Feb 27.
A number of platinum(II) complexes with steric hindrance derived from (1R,2R)-N(1)-benzylcyclohexane-1,2-diamine derivatives were designed and prepared. Biological assay indicated that most complexes showed antitumor activity against the tested cancer cell lines, especially those with chloride anions as leaving groups had compatible or superior activity to cisplatin and oxaliplatin. Complex 2a, as the most potent agent, is also sensitive to cisplatin resistant SGC7901/CDDP cancer cell line, which has been subsequently studied by cellular uptake, flow cytometry, gel electrophoresis and western blot assays. The steric hindrance resulting from a pending 2-fluorobenzyl moiety of the ligand might be the key factor for its ability to overcome cisplatin resistant cancer cells.
一些具有位阻的铂(II)配合物是由（1R,2R）-N(1)-苄基环己烷-1,2-二胺衍生物衍生而来的，被设计并制备。生物测定表明，大多数配合物对测试的癌细胞系表现出抗肿瘤活性，特别是那些具有氯离子作为离去基团的配合物与顺铂和奥沙利铂具有相当或更高的活性。配合物 2a 是最有效的药物，对顺铂耐药的 SGC7901/CDDP 癌细胞系也敏感，随后通过细胞摄取、流式细胞术、凝胶电泳和 Western blot 分析进行了研究。配体中悬垂的 2-氟苄基部分引起的空间位阻可能是其克服顺铂耐药癌细胞的能力的关键因素。
