Pandey Shivendra Kumar, Kumar Sandeep, Singh Swati, Patel Anand Kumar, Gond Mannu Kumar, Acharya Arbind, Bharty Manoj Kumar
Department of Chemistry, Banaras Hindu University, Varanasi 221005, India.
Department of Zoology, Banaras Hindu University, Varanasi 221005, India.
Dalton Trans. 2025 Jan 13;54(3):1139-1149. doi: 10.1039/d4dt02614d.
Cancer is a prominent global cause of mortality. Palladium complexes have the potential to serve as effective anticancer and pharmacological agents, offering a viable alternative to platinum medications. This work focused on the development of a new thiolato-bridged dinuclear [Pd(M3MPyThU)Cl]2 and mononuclear palladium [Pd(M3MPyThU)2] complexes containing 1-methyl-3-(3-methylpyridin-2-yl) thiourea (HM3MPyThU) ligand. The prepared ligand and complexes have been fully characterised by various spectroscopic and single-crystal crystallographic data. The ligand and complexes were further examined for their anticancer activities against the HT-29 (human colon) and MCF-7 (human breast) cancer cells along with the standard drug cisplatin, and the outcome suggests that tested compounds have a better cytotoxic response against HT-29 cells. The order of anticancer activity was found as [Pd(M3MPyThU)Cl]2 > cisplatin > [Pd(M3MPyThU)2] > HM3MPyThU. The complex [Pd(M3MPyThU)Cl]2 demonstrated potent cytotoxic effects against HT-29 cells with an IC value of 10 ± 3.3 μM. The comparison of the anticancer activity of the described complexes with previous reports on HT-29 cells suggests that the described complexes have better anticancer activity than previously reported complexes. Further assays were performed for [Pd(M3MPyThU)Cl]2 to gain insights into the mechanism of cell death and found that reduced mitochondrial membrane potential and increased ROS production, highlighting mitochondrial-dependent apoptosis as the major mechanism for tumour cell death. Additionally, [Pd(M3MPyThU)Cl]2 was found to be more selective compared to cisplatin since it exhibited decreased toxicity towards healthy cells (HEK-293).
癌症是全球主要的死亡原因。钯配合物有潜力成为有效的抗癌和药理剂,为铂类药物提供了一种可行的替代方案。这项工作聚焦于开发一种新的硫醇盐桥联双核[Pd(M3MPyThU)Cl]2和单核钯[Pd(M3MPyThU)2]配合物,其含有1-甲基-3-(3-甲基吡啶-2-基)硫脲(HM3MPyThU)配体。所制备的配体和配合物已通过各种光谱和单晶晶体学数据进行了全面表征。该配体和配合物还与标准药物顺铂一起,针对HT-29(人结肠)和MCF-7(人乳腺)癌细胞进行了抗癌活性检测,结果表明所测试的化合物对HT-29细胞具有更好的细胞毒性反应。发现抗癌活性顺序为[Pd(M3MPyThU)Cl]2 > 顺铂 > [Pd(M3MPyThU)2] > HM3MPyThU。配合物[Pd(M3MPyThU)Cl]2对HT-29细胞表现出强效的细胞毒性作用,IC值为10 ± 3.3 μM。将所描述配合物的抗癌活性与先前关于HT-29细胞的报道进行比较表明,所描述的配合物比先前报道的配合物具有更好的抗癌活性。对[Pd(M3MPyThU)Cl]2进行了进一步检测以深入了解细胞死亡机制,发现线粒体膜电位降低和活性氧生成增加,突出了线粒体依赖性凋亡是肿瘤细胞死亡的主要机制。此外,发现[Pd(M3MPyThU)Cl]2与顺铂相比更具选择性,因为它对健康细胞(HEK-293)的毒性较低。