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新型含 N-磺酰胺配体的铜配合物:具有抗肿瘤、抗菌和抗氧化活性的潜在药物。

New Cu Complexes with N-Sulfonamide Ligands: Potential Antitumor, Antibacterial, and Antioxidant Agents.

机构信息

Department of Inorganic Chemistry, Faculty of Pharmacy, "Iuliu-Hațieganu" University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania.

National Institute for Research and Development of Isotopic and Molecular Technologies, 400293 Cluj-Napoca, Romania.

出版信息

Molecules. 2022 May 23;27(10):3338. doi: 10.3390/molecules27103338.

Abstract

Nowadays, the discovery of a new non-toxic metal complex with biological activity represents a very active area of research. Two Cu complexes, [Cu(L1)(HO)] (C1) (HL1= N-(5-(4-methylphenyl)-[1,3,4]-thiadiazole-2-yl)-naphtalenesulfonamide) and [Cu(L2)(py)(HO)] (C2) (HL2= N-(5-ethyl-[1,3,4]-thiadiazole-2-yl)-naphtalenesulfonamide), with two new ligands were synthesized. The X-ray crystal structures of the complexes were determined. In both complexes, Cu is five-coordinated, forming a CuNO and CuNO chromophore, respectively. The ligands act as monodentate, coordinating the metal ion through a single N atom; for the C2 complex, the molecules from the reaction medium (pyridine and water) are also involved in the coordination of Cu. The complexes have a distorted square pyramidal square-planar geometry. The compounds were characterized by FT-IR, electronic EPR spectroscopy, and magnetic methods. The nuclease activity studies confirm the complexes' capacity to cleave the DNA molecule. Using a xanthine-xanthine oxydase system, the SOD mimetic activity of the complexes was demonstrated. Cytotoxicity studies were carried out on two tumor cell lines (HeLa, WM35) and on a normal cell line (HFL1) using the MTT method, with cisplatin used as a positive control. The antibacterial activity of the complexes was investigated against two Gram-positive and two Gram-negative bacteria, and compared with Amoxicillin and Norfloxacin using the disk diffusion method. Both complexes showed in vitro biological activity but the C2 complex was more active. A lack of in vivo toxicity was demonstrated for the C2 complex by performing hepatic, renal, and hematological studies on Swiss mice.

摘要

如今,发现具有生物活性的新型无毒金属配合物是一个非常活跃的研究领域。合成了两种含有两个新配体的 Cu 配合物[Cu(L1)(HO)](C1)(HL1=N-(5-(4-甲基苯基)-[1,3,4]-噻二唑-2-基)萘磺酰胺)和[Cu(L2)(py)(HO)](C2)(HL2=N-(5-乙基-[1,3,4]-噻二唑-2-基)萘磺酰胺)。通过 X 射线晶体结构确定了配合物的结构。在这两个配合物中,Cu 均为五配位,分别形成 CuNO 和 CuNO 发色团。配体作为单齿配体,通过单个 N 原子与金属离子配位;对于 C2 配合物,来自反应介质(吡啶和水)的分子也参与 Cu 的配位。配合物具有扭曲的四方锥平面四方构型。通过 FT-IR、电子顺磁共振光谱和磁性方法对化合物进行了表征。对配合物的核酸酶活性研究证实了它们切割 DNA 分子的能力。使用黄嘌呤-黄嘌呤氧化酶体系,证明了配合物的 SOD 模拟活性。使用 MTT 法对两种肿瘤细胞系(HeLa、WM35)和一种正常细胞系(HFL1)进行了细胞毒性研究,顺铂作为阳性对照。采用圆盘扩散法,研究了配合物对两种革兰氏阳性菌和两种革兰氏阴性菌的抗菌活性,并与阿莫西林和诺氟沙星进行了比较。两种配合物均显示出体外生物活性,但 C2 配合物的活性更高。通过对瑞士小鼠进行肝、肾和血液学研究,证明了 C2 配合物体内无毒性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9751/9144936/a01825523165/molecules-27-03338-g001.jpg

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