Department of Chemistry, Quaid-i-Azam University, Islamabad, 45320, Pakistan; School of Chemistry, Trinity College Dublin, Dublin 2, Ireland.
School of Chemistry, Trinity Biomedical Sciences Institute, Trinity College Dublin, 152-160 Pearse Street, Dublin 2, Ireland.
Eur J Med Chem. 2019 Nov 1;181:111544. doi: 10.1016/j.ejmech.2019.07.047. Epub 2019 Jul 16.
There is a growing interest in the cancer cell growth inhibitory effects of organotin (IV) compounds and, accordingly, a new series of dimethyl-, di-(n-butyl)-, diphenyl- and chloro-phenyl tin(IV) complexes with a Schiff base core were prepared. Their binding to DNA was assessed by UV thermal denaturation showing no interaction and by UV-vis titration exhibiting moderate interaction by intercalation. Complexes having n-butyl substituents were more potent and cytotoxic against human leukemia, breast and cervical cancer cell lines than other organotin(IV) complexes tested. Unfortunately, some of these compounds showed similar cytotoxicity in a non-cancerous cell line. We may conclude that cytotoxic activity was dependent on the nature (lipophilicity and size, according to the structure-activity relationship studies) and substitution pattern on the different structures. These results may aid in the rational design of metallodrugs, expanding the scope of organotin complexes in formulating new metal based drugs with dibutyl moieties.
人们对有机锡（IV）化合物抑制癌细胞生长的作用越来越感兴趣，因此，我们合成了一系列带有席夫碱核心的新的二甲基、二（正丁基）、二苯基和氯苯基锡（IV）配合物。通过紫外光热变性实验表明它们与 DNA 没有相互作用，通过紫外可见滴定实验表明它们通过插入方式进行中等强度的相互作用。具有正丁基取代基的配合物对人白血病、乳腺癌和宫颈癌细胞系的抑制作用比其他测试的有机锡（IV）配合物更强、更具细胞毒性。不幸的是，其中一些化合物在非癌细胞系中表现出相似的细胞毒性。我们可以得出结论，细胞毒性活性取决于不同结构的性质（根据构效关系研究，亲脂性和大小）和取代模式。这些结果可能有助于合理设计金属药物，扩大含二丁基部分的有机锡配合物在制定新型金属基药物方面的应用范围。
