University of Belgrade - Faculty of Chemistry, Studentski Trg 12-16, 11000, Belgrade, Serbia.
Department of Pharmaceutical Technology and Biochemistry, Faculty of Chemistry, Gdansk University Technology, Narutowicza 11/12, 80-233, Gdansk, Poland.
Eur J Med Chem. 2022 Aug 5;238:114449. doi: 10.1016/j.ejmech.2022.114449. Epub 2022 May 12.
The biological activity of Cd compounds has been investigated scarce since Cd has been recognized as a human carcinogen. However, the toxicity of cadmium is comparable to the toxicity of noble metals such as Pt and Pd. The paradigm of metal toxicity has been challenged suggesting that metal toxicity is not a constant property, yet it depends on many factors like the presence of appropriate ligands. Studies on anticancer activity of cadmium complexes showed that the complexation of various ligands resulted in complexes that showed better activities than approved drugs. In the present study, cadmium complexes with biologically potent thiazolyl/selenazoyl-hydrazone ligands have been prepared, and tested for their activity against different types of tumor cell models. The complexation of ligands with Cd(II) resulted in a synergistic effect. The antiproliferative activity study revealed that all complexes are more active compared to 5-fluorouracil and cisplatin. The mechanism of tumor cell growth inhibition reveal that selenium-based compounds induce cell death in T-47D (gland carcinoma) cells through apoptosis via caspase-3/7 activation. Additionally, their pro-apoptotic effect was stronger compared to etoposide and cisplatin. Nuclease activity, detected by gel electrophoresis, may be the possible mechanism of anticancer action of investigated complexes.
由于镉已被确认为人类致癌物,因此对其化合物的生物活性的研究很少。然而,镉的毒性与铂和钯等贵金属的毒性相当。金属毒性的范例受到了挑战,这表明金属毒性不是一个恒定的特性,而是取决于许多因素,例如是否存在合适的配体。关于镉配合物的抗癌活性的研究表明,与各种配体的络合导致了显示出比批准药物更好活性的配合物。在本研究中,制备了具有生物活性的噻唑基/硒唑基酰腙配体的镉配合物,并对其针对不同类型的肿瘤细胞模型的活性进行了测试。配体与 Cd(II)的络合产生了协同作用。增殖活性研究表明,与 5-氟尿嘧啶和顺铂相比,所有配合物均更具活性。肿瘤细胞生长抑制的机制表明,基于硒的化合物通过 caspase-3/7 激活诱导 T-47D(腺癌)细胞通过细胞凋亡发生细胞死亡。此外,与依托泊苷和顺铂相比,它们的促凋亡作用更强。通过凝胶电泳检测到的核酸酶活性可能是所研究配合物的抗癌作用的可能机制。