Bulatov Emil, Sayarova Regina, Mingaleeva Rimma, Miftakhova Regina, Gomzikova Marina, Ignatyev Yuri, Petukhov Alexey, Davidovich Pavel, Rizvanov Albert, Barlev Nickolai A
1Kazan Federal University, Kazan, Russian Federation.
2Institute of Cytology of Russian Academy of Sciences, St. Petersburg, Russian Federation.
Cell Death Discov. 2018 Nov 13;4:103. doi: 10.1038/s41420-018-0120-z. eCollection 2018.
Medicinal bioinorganic chemistry is a thriving field of drug research for cancer treatment. Transition metal complexes coordinated to essential biological scaffolds represent a highly promising class of compounds for design of novel target-specific therapeutics. We report here the biological evaluation of a novel Isatin-Schiff base derivative and its Cu(II) complex in several tumor cell lines by assessing their effects on cellular metabolism, real-time cell proliferation and induction of apoptosis. Further, the impact of compounds on the p53 protein and expression of its target genes, including , , and was evaluated. Results obtained in this study provide further evidence in support of our prior data suggesting the p53-mediated mechanism of action for Isatin-Schiff base derivatives and their complexes and also shed light on potential use of these compounds for stimulation of apoptosis in breast cancer cells via activation of the pro-apoptotic gene.
药物生物无机化学是癌症治疗药物研究中一个蓬勃发展的领域。与重要生物支架配位的过渡金属配合物是一类极具潜力的化合物,可用于设计新型靶向特异性治疗药物。我们在此报告一种新型异吲哚酮-席夫碱衍生物及其铜(II)配合物在几种肿瘤细胞系中的生物学评价,通过评估它们对细胞代谢、实时细胞增殖和细胞凋亡诱导的影响。此外,还评估了这些化合物对p53蛋白及其靶基因(包括、和)表达的影响。本研究获得的结果进一步支持了我们之前的数据,表明异吲哚酮-席夫碱衍生物及其配合物的作用机制是由p53介导的,同时也揭示了这些化合物通过激活促凋亡基因来刺激乳腺癌细胞凋亡的潜在用途。