有机硒反式钯(II)配合物的合成、表征及生物学研究。

Synthesis, Characterization and Biological Studies of Organoselenium trans-Palladium(II) Complexes.

机构信息

University of Kragujevac, Faculty of Medical Sciences, Svetozara Markovica 69, Kragujevac, 34000, Serbia.

Department of Chemistry, Faculty of Science, University of Kragujevac, Radoja Domanovica 12, Kragujevac, 34000, Serbia.

出版信息

Med Chem. 2021;17(9):1007-1022. doi: 10.2174/1573406416666200930112442.

DOI:10.2174/1573406416666200930112442

PMID:32998677

Abstract

BACKGROUND

Over the years, transition metal complexes have exhibited significant antimicrobial and antitumor activity. It all started with cisplatin discovery, but due to the large number of side effects it shows, there is a growing need to find a new metal-based compound with higher selectivity and activity on more tumors.

OBJECTIVES

Two novel trans-palladium(II) complexes with organoselenium compounds as ligands, [Pd(L1)Cl] (L1 = 5-(phenylselanylmethyl)-dihydrofuran-2(3H)-one) and [Pd(L2)Cl] (L2 = 2- methyl-5-(phenylselanylmethyl)- tetrahydrofuran) were synthesized, in the text referred to as Pd-Se1 and Pd-Se2. Also, a structurally similar trans-palladium(II) complex, [Pd(L3)Cl] (L3= 2,2- dimethyl-3-(phenylselanylmethyl)-tetrahydro-2H-pyran) was synthesized according to an already published work and is referred to as Pd-Se3. The interaction of synthesized complexes with DNA and bovine serum albumin was observed. Also, antimicrobial activity and in vitro testing, cell viability, and cytotoxic effects of synthesized ligands and complexes on human epithelial colorectal cancer cell line HCT-116 were studied. Molecular docking simulations were performed to understand better the binding modes of the complexes reported in this paper with DNA and BSA, as well as to comprehend their antimicrobial activity.

METHODS

The interactions of the synthesized complexes with DNA and bovine serum albumin were done using UV-Vis and emission spectral studies as well as docking studies. Antimicrobial activity was tested by determining the minimum inhibitory concentrations (MIC) and minimum microbicidal concentration (MMC) using the resazurin microdilution plate method. Cytotoxic activity on cancer cells was studied by MTT test.

RESULTS

The Pd(II) complexes showed a significant binding affinity for calf thymus DNA and bovine serum albumin by UV-Vis and emission spectral studies. The intensity of antimicrobial activity varied with the complexes Pd-Se1 and Pd-Se3, showing significantly higher activity than the corresponding ligand. The most significant activity was shown on Pseudomonas aeruginosa. Under standardized laboratory conditions for in vitro testing, cell viability and cytotoxic effects of synthesized ligands and complexes were studied on human epithelial colorectal cancer cell line HCT-116, where Pd-Se2 showed some significant cytotoxic effects.

CONCLUSION

The newly synthesized complexes have the potential to be further investigated as metallodrugs.

摘要

背景

多年来，过渡金属配合物表现出显著的抗菌和抗肿瘤活性。这一切都始于顺铂的发现，但由于它表现出大量的副作用，因此越来越需要找到一种新的基于金属的化合物，对更多的肿瘤具有更高的选择性和活性。

目的

合成了两种新型的反式钯（II）配合物，配体为有机硒化合物，[Pd（L1）Cl]（L1=5-（苯硒基甲基）-二氢呋喃-2（3H）-酮）和[Pd（L2）Cl]（L2=2-甲基-5-（苯硒基甲基）-四氢呋喃），在文中分别称为 Pd-Se1 和 Pd-Se2。此外，还根据已发表的工作合成了结构相似的反式钯（II）配合物[Pd（L3）Cl]（L3=2,2-二甲基-3-（苯硒基甲基）-四氢-2H-吡喃），并称为 Pd-Se3。观察了合成配合物与 DNA 和牛血清白蛋白的相互作用。还研究了合成配体和配合物对人结肠直肠癌细胞系 HCT-116 的抗菌活性和体外测试、细胞活力和细胞毒性作用。进行了分子对接模拟，以更好地理解本文报道的配合物与 DNA 和 BSA 的结合模式，并理解它们的抗菌活性。

方法

通过紫外-可见和荧光光谱研究以及对接研究，研究了合成配合物与 DNA 和牛血清白蛋白的相互作用。采用 Resazurin 微量稀释板法测定最小抑菌浓度（MIC）和最小杀菌浓度（MMC）来测定抗菌活性。通过 MTT 试验研究了对癌细胞的细胞毒性。

结果

钯（II）配合物通过紫外-可见和荧光光谱研究显示出与小牛胸腺 DNA 和牛血清白蛋白的显著结合亲和力。抗菌活性的强度因配合物 Pd-Se1 和 Pd-Se3 而异，显示出比相应配体显著更高的活性。对铜绿假单胞菌的活性最高。在标准化的体外测试实验室条件下，研究了合成配体和配合物对人结肠直肠癌细胞系 HCT-116 的细胞活力和细胞毒性作用，其中 Pd-Se2 表现出一些显著的细胞毒性作用。