2-Aminophenol-based ligands and Cu(II) complexes: Synthesis, characterization, X-ray structure, thermal and electrochemical properties, and in vitro biological evaluation, ADMET study and molecular docking simulation
2-Aminophenol-based ligands and Cu(II) complexes: Synthesis, characterization, X-ray structure, thermal and electrochemical properties, and in vitro biological evaluation, ADMET study and molecular docking simulation
复制标题
DOI：
10.1016/j.molstruc.2022.134073
复制
发表时间：
2022-09-08
影响因子：
3.8
通讯作者：
Cesme, Mustafa
中科院分区：
文献类型：
--
作者：
Cesme, Mustafa
合成了两种配体2-[(2,4-二甲氧基亚苄基)氨基]苯酚(HA)、2-[(2,5-二甲氧基亚苯亚甲基)氨基]苯酚(HB)及其Cu2+过渡金属配合物,并通过元素分析、质谱、UV-vis、1 H和 13 C NMR(仅用于HA和HB)和FTIR方法进行了表征。从乙醇溶液中获得了配体HA和HB的单晶，单晶X射线衍射技术阐明了它们的分子结构。使用热重分析 (TGA) 和差热分析 (DTA) 方法研究了 2-氨基苯酚基配体（HA 和 HB）及其 Cu2+ 金属配合物的热性质。所有化合物的电化学性质均在-1.1 至+1.1 V 范围内进行了研究。针对两种革兰氏阳性菌（金黄色葡萄球菌和蜡样芽孢杆菌）、两种革兰氏阴性菌（大肠杆菌和鼠伤寒沙门氏菌）和一种真菌菌株（白色念珠菌）筛选了体外抗菌活性，并且化合物表现出杀菌和杀真菌行为。通过计算两种细胞类型的 IC50 值，评估了化合物对 HUVEC 和 MCF-7 细胞的细胞毒性特性。所测试的化合物在MCF-7细胞系中HA化合物的最小IC50值为34.19μM，而在HUVEC细胞系中HB化合物的最小IC50值为17.67μM。除了湿式实验室研究外，还对化合物的 ADMET 特性进行了彻底评估，没有发现任何化合物违反任何药物相似性规则。根据 ADMET 数据，合成化合物的理化和药理学特性保持在 Lipinski 的 RO5 预测限值内，并且具有高生物利用度。计算机毒性研究表明，这些化合物没有表现出 AMES 毒性和肝毒性。在计算机上，对化合物的靶受体进行了预测，它们作为激酶抑制剂的潜力很高。因此，选择BRAF（V600E）蛋白激酶作为分子对接研究的靶蛋白。分子对接研究表明，所有化合物都对酶活性位点的关键残基表现出显着的亲和力，证实了 BRAF (V600E) 蛋白激酶的抑制性质，显示出极性和非极性相互作用。 (c) 2022 Elsevier B.V. 保留所有权利。
Two ligands 2-[(2,4-dimethoxybenzylidene )amino]phenol (HA), 2-[(2,5-dimethoxybenzylidene )amino]phenol (HB) and their Cu2+ transition metal complexes were synthesized and characterized by elemental anal-ysis, mass spectra, UV-vis, 1 H and 13 C NMR (only used for HA and HB) and FTIR methods. Single crys-tals of the ligands HA and HB were obtained from ethanol solution, and single-crystal X-ray diffraction techniques have elucidated their molecular structures. Thermal properties of the 2-amino phenol-based ligands (HA and HB) and their Cu2+ metal complexes have been investigated by using thermogravimetric (TGA) and differential thermal analyses (DTA) methods. The electrochemical properties of all compounds have been studied in the-1.1 to + 1.1 V range. In vitro antimicrobial activity was screened against two gram-positive ( Staphylococcus aureus and Bacillus cereus), two gram-negative (Escherichia coli and S. ty-phimurium), and one fungal strain (Candida albicans) and compounds exhibited bactericidal and fungici-dal behavior. The cytotoxic properties of the compounds were evaluated on HUVEC and MCF-7 cells by calculating IC50 values for both cell types. The smallest IC50 values of the compounds tested were 34.19 mu M for the HA compound in the MCF-7 cell line, while they were calculated to be 17.67 mu M for the HB compound in the HUVEC cell line. In addition to the wet laboratory investigations, the ADMET characteristics of the compounds were thoroughly assessed, and none of them were found to violate any drug similarity rules. The synthesized compounds' physicochemical and pharmacological characteristics stayed within Lipinski's RO5 projected limits and have a high bioavailability profile according to ADMET data. In silico toxicity studies revealed that the compounds did not show AMES toxicity and hepato-toxicity. In silico, target receptor predictions of the compounds were performed, and their potential to be kinase inhibitors was high. Therefore, BRAF (V600E) protein kinase was selected target protein in molecu-lar docking studies. Molecular docking studies revealed that all compounds exhibited a significant affinity for crucial residues in the enzyme's active site, confirming the inhibitory nature of BRAF (V600E) protein kinase, showing both polar and apolar interactions. (c) 2022 Elsevier B.V. All rights reserved.