In this work we synthesized a chelating Schiff base by a single condensation of salicylaldehyde with 3,4-diamino benzoic acid (1). This ligand was used further for complexation to CoCl2·6H2O under nitrogen. In the next step, three six-coordinate Co(III) complexes were synthesized by coordinating this complex with imidazole (2), 2-methyimidazole (3) and N-Boc-l-histidine methyl ester (4) (Boc: tert.-butoxycarbonyl) in axial positions with simultaneous oxidation of Co(II) to Co(III) under ambient environment. All Co(III) complexes were characterized by multinuclear NMR spectroscopy (1H, 13C and 59Co NMR), FT-IR, mass spectrometry and HPLC. The Co(III) complexes were conjugated to three different cell penetrating peptides: FFFF (P1), RRRRRRRRRGAL (P2) and FFFFRRRRRRRRRGAL (P3). Standard solid-phase peptide chemistry was used for the synthesis of cell penetrating peptides. Coupling of N-terminal peptides with the cobalt complexes, possessing a carboxylic group on the tetradentate Schiff base ligand, afforded Co(III)-peptide bioconjugates, which were purified by semi-preparative HPLC and characterized by analytical HPLC and mass spectrometry. The antiproliferative activity of the synthesized compounds was studied against different human tumour cell lines: lung cancer A549, liver cancer HepG2 and normal human fibroblasts GM5657T, in comparison with the activity of cisplatin as a reference drug. The bioconjugate 21 containing the Co complex 4 and the combined phenylalanine and polyarginine cell penetrating sequence P3 shows better activity against the liver cancer line HepG2 than the parent Co(III) complex 4.

中文翻译：

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Co（III）配合物与席夫碱配体和细胞穿透肽的生物共轭物：固相合成，表征和抗增殖活性。

在这项工作中，我们通过水杨醛与3,4-二氨基苯甲酸（1）的单缩合反应合成了一种螯合的席夫碱。该配体在氮气下进一步用于与CoCl2·6H2O络合。在下一步中，通过使该配合物与咪唑（2），2-甲基咪唑（3）和N-Boc-1-组氨酸甲酯（4）配位（Boc：叔。 -丁氧基羰基）在轴向位置，同时在环境中将Co（II）氧化为Co（III）。所有的Co（III）配合物均通过多核NMR光谱（1H，13C和59Co NMR），FT-IR，质谱和HPLC进行表征。Co（III）复合物与三种不同的细胞穿透肽偶联：FFFF（P1），RRRRRRRRRRGAL（P2）和FFFFRRRRRRRRRGAL（P3）。标准固相肽化学用于细胞穿透肽的合成。N末端肽与钴配合物的偶联，在四齿席夫碱配体上具有羧基，提供了Co（III）-肽生物缀合物，其通过半制备HPLC纯化并通过分析HPLC和质谱法表征。与顺铂作为参考药物的活性相比，研究了合成化合物对不同人类肿瘤细胞系（肺癌A549，肝癌HepG2和正常人成纤维细胞GM5657T）的抗增殖活性。含有Co配合物4以及苯丙氨酸和聚精氨酸细胞穿透序列P3的生物共轭物21对母体Co（III）配合物4的抗肝癌HepG2活性更高。