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苯并咪唑衍生物与镉的新型配位化合物的设计、合成与表征

Design, Synthesis, and Characterization of Novel Coordination Compounds of Benzimidazole Derivatives with Cadmium.

作者信息

Raducka Anita, Świątkowski Marcin, Korona-Głowniak Izabela, Kaproń Barbara, Plech Tomasz, Szczesio Małgorzata, Gobis Katarzyna, Czylkowska Agnieszka

机构信息

Institute of General and Ecological Chemistry, Faculty of Chemistry, Lodz University of Technology, Żeromskiego 116, 90-924 Łódź, Poland.

Department of Pharmaceutical Microbiology, Medical University of Lublin, Chodźki 1, 20-093 Lublin, Poland.

出版信息

Pharmaceutics. 2022 Aug 3;14(8):1626. doi: 10.3390/pharmaceutics14081626.

Abstract

Four complexes of Cd(II) with benzimidazole derivatives were synthesized and named C1, C2, C3, and C4. All coordination compounds were characterized through elemental analysis (EA), flame atomic absorption spectrometry (FAAS), Fourier-transform infrared spectroscopy (FTIR), thermogravimetric analysis coupled with mass spectrometry) (TG-MS), a cytotoxicity assay (MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide)), and computational chemical analysis for absorption, distribution, metabolism, and excretion (ADME). All of the obtained results are compatible and are consistent with the respective structures of the obtained compounds and their properties. The various techniques used allowed the determination of the composition, proposed structure of the compounds, their thermal stability and thermal properties, and the method of coordination between the metal (II) ion and the ligand. The ADME technique was also used to estimate the physicochemical and biological properties. The antitumor activity of the compounds was determined with an MTT assay on the glioblastoma (T98G), neuroblastoma (SK-N-AS), and lung adenocarcinoma (A549) cell lines, as well as normal human skin fibroblasts (CCD-1059Sk). Compound C2 was found to have potential antitumor properties and to be effective in inhibiting the growth of neuroblastoma cells. The antimicrobial activity of Cd complexes, free ligands, and reference drugs was tested against six strains of Gram-positive bacteria, five strains of Gram-negative rods, and three strains of yeasts. Compound C3 significantly increased activity against Gram-positive bacteria in comparison to the ligand.

摘要

合成了四种镉(II)与苯并咪唑衍生物的配合物,分别命名为C1、C2、C3和C4。所有配位化合物均通过元素分析(EA)、火焰原子吸收光谱法(FAAS)、傅里叶变换红外光谱法(FTIR)、热重分析联用质谱法(TG-MS)、细胞毒性测定(MTT(3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐))以及吸收、分布、代谢和排泄(ADME)的计算化学分析进行了表征。所有获得的结果相互兼容,与所得到化合物的各自结构及其性质一致。所使用的各种技术能够确定化合物的组成、推测结构、热稳定性和热性质,以及金属(II)离子与配体之间的配位方式。ADME技术还用于评估物理化学和生物学性质。通过MTT法在胶质母细胞瘤(T98G)、神经母细胞瘤(SK-N-AS)、肺腺癌(A549)细胞系以及正常人皮肤成纤维细胞(CCD-1059Sk)上测定了化合物的抗肿瘤活性。发现化合物C2具有潜在的抗肿瘤特性,并且在抑制神经母细胞瘤细胞生长方面有效。测试了镉配合物、游离配体和参考药物对六种革兰氏阳性菌、五种革兰氏阴性杆菌和三种酵母菌株的抗菌活性。与配体相比,化合物C3对革兰氏阳性菌的活性显著增强。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b0ca/9412362/bf21dbb58477/pharmaceutics-14-01626-sch001.jpg

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