Department of Chemical Technologies, Iranian Research Organization for Science and Technology (IROST), Tehran, Iran.
Department of Biotechnology, Iranian Research Organization for Science and Technology (IROST), Tehran, Iran.
Bioorg Chem. 2024 Oct;151:107634. doi: 10.1016/j.bioorg.2024.107634. Epub 2024 Jul 14.
Nicotinamide, known as Vitamin-B3, has shown promising potential in improving various medical conditions. Carbacylamidophosphates (CAPh) are versatile phosphoramide ligands with a wide range of applications in both biochemistry and chemistry. Herein, to obtain compounds with enhanced anticancer activity and study the effect of the structure on this activity, four new Co(II) complexes of vitaminB3-based CAPh ligands with the formula of CoCl3-NCHCONHPO(NCH), CoCl3-NCHCONHPO(NCHCH), CoCl3-NCHCONHPO(NCH), and CoCl3-NCHCONHPO(NCH) were designed and synthesized. FT-IR, UV-Vis, Atomic Absorption (AAS),H, C, and PNMR, and Mass spectroscopies beside CHN and Molar conductivity methods were utilized to characterize the synthesized compounds. Using MTT-assay and Flow Cytometry, the anticancer effects of these complexes were studied on three distinct cell lines, including one normal cell line (MCF10A) and two cancer cell lines (MDA-MB-231, MCF-7). Results showed that our ligands could form complexes by coordinating with cobalt, which, not only have a very strong killing effect on cancer cells but also have a higher level of safety for normal cells and are more cost-efficient than Cisplatin. C was the most effective complex at inhibiting the growth of MCF-7 and MDA-MB-231 cells which exhibited a remarkable 97.5 % reduction in cancer cell growth and a Selectivity Index up to > 37. This is an impressive 93 and 54 times more selective and safer than commonly used drugs like Cisplatin and Doxorubicin, respectively.Flow Cytometry analysis shows complex-induced breast cancer cell apoptosis.The ligands' amine structure and ring size can directly impact the complexes' anticancer effect and safety for normal cells.
烟酰胺,又称维生素 B3,已显示出在改善多种医学病症方面的巨大潜力。氨基甲酰基膦酸盐(CAPh)是一种多功能的膦酰胺配体,在生物化学和化学领域都有广泛的应用。在此,为了获得具有增强的抗癌活性的化合物,并研究结构对这种活性的影响,我们设计并合成了四种基于维生素 B3 的 CAPh 配体与 Co(II) 的配合物,其化学式为 CoCl3-NCHCONHPO(NCH)、CoCl3-NCHCONHPO(NCHCH)、CoCl3-NCHCONHPO(NCH)和 CoCl3-NCHCONHPO(NCH)。利用 FT-IR、UV-Vis、原子吸收光谱(AAS)、H、C、PNMR 和质谱以及元素分析和摩尔电导率方法对合成的化合物进行了表征。通过 MTT 分析和流式细胞术,研究了这些配合物对三种不同细胞系(包括一种正常细胞系(MCF10A)和两种癌细胞系(MDA-MB-231、MCF-7)的抗癌作用。结果表明,我们的配体可以通过与钴配位形成配合物,这些配合物不仅对癌细胞具有很强的杀伤作用,而且对正常细胞的安全性更高,而且比顺铂更具成本效益。C 是抑制 MCF-7 和 MDA-MB-231 细胞生长最有效的配合物,对癌细胞生长的抑制率高达 97.5%,选择性指数高达>37。与顺铂和多柔比星等常用药物相比,这分别提高了 93 倍和 54 倍的选择性和安全性。流式细胞术分析表明,配合物诱导乳腺癌细胞凋亡。配体的胺结构和环大小可以直接影响配合物的抗癌作用和对正常细胞的安全性。