Department of Chemistry, North Tehran Branch, Islamic Azad University, Tehran, 19585-936, Iran.
Department of Toxicology & Pharmacology, University of Tehran Medical Sciences, Tehran, 14155-6451, Iran.
Cell Biochem Biophys. 2020 Dec;78(4):521-529. doi: 10.1007/s12013-020-00937-y. Epub 2020 Aug 27.
Pt-based drugs such as cisplatin are frontline drugs used for the treatment of different solid malignancies. However, they represent major problems, such as severe side effects and drug resistance. To find out the structure-activity relationship; in this study, Pt(II) and Pt(IV) complexes with similar ligands, namely tetrachloro(2,2'-dipyridylamine)platinum(IV) (1) and dichloro(2,2'-dipyridylamine)platinum(II) (2) were synthesized, tested for their in vitro activity over different tumor cell lines and compared with cisplatin. Despite nontoxicity against nonmalignant cells, both titled compounds depict considerable killing activity over HT-29 cells. So, this cell line is served for further investigation. Cell cycle test revealed that the mechanism of cell cycle arrest induced by complexes 1 and 2 over HT-29 cells was relatively similar and obviously different from cisplatin. Moreover, apoptosis analysis showed that late apoptosis/necrosis is the primary disease for the death of cell by three complexes. Comet assay and colony-forming test were also performed on HT-29 cells whose results were thoroughly discussed.
基于铂的药物，如顺铂，是治疗不同实体恶性肿瘤的一线药物。然而，它们存在严重的副作用和耐药性等问题。为了找出结构-活性关系，本研究合成了具有相似配体的 Pt(II) 和 Pt(IV) 配合物，即四氯(2,2'-联吡啶胺)铂(IV)(1)和二氯(2,2'-联吡啶胺)铂(II)(2)，并对其在不同肿瘤细胞系中的体外活性进行了测试，并与顺铂进行了比较。尽管这两种标题化合物对非恶性细胞没有毒性，但它们对 HT-29 细胞都具有相当大的杀伤活性。因此，选择该细胞系进行进一步研究。细胞周期试验表明，复合物 1 和 2 诱导 HT-29 细胞周期停滞的机制相对相似，与顺铂明显不同。此外，凋亡分析表明，三种复合物导致细胞死亡的主要原因是晚期凋亡/坏死。彗星试验和集落形成试验也在 HT-29 细胞上进行，对结果进行了深入讨论。
