Department of Chemistry, College of Science, University Ha'il, Ha'il 81451, Saudi Arabia.
Department of Science, Institute for Information Technologies, University of Kragujevac, Jovana Cvijića bb, 34000 Kragujevac, Serbia.
Int J Mol Sci. 2023 Sep 29;24(19):14745. doi: 10.3390/ijms241914745.
Pyridoxylidene-aminoguanidine (PLAG) and its transition metal complexes are biologically active compounds with interesting properties. In this contribution, three new metal-PLAG complexes, Zn(PLAG)(SO)(HO)].∙HO (Zn-PLAG), [Co(PLAG)]SO∙2HO (Co-PLAG), and [Fe(PLAG)]SO∙2HO) (Fe-PLAG), were synthetized and characterized by the X-ray crystallography. The intermolecular interactions governing the stability of crystal structure were compared to those of Cu(PLAG)(NCS) (Cu-PLAG) within Hirshfeld surface analysis. The structures were optimized at B3LYP/6-31+G(d,p)(H,C,N,O,S)/LanL2DZ (Fe,Co,Zn,Cu), and stability was assessed through Natural Bond Orbital Theory and Quantum Theory of Atoms in Molecules. Special emphasis was put on investigating the ligand's stability and reactivity. The binding of these compounds to Bovine and Human serum albumin was investigated by spectrofluorometric titration. The importance of complex geometry and various ligands for protein binding was shown. These results were complemented by the molecular docking study to elucidate the most important interactions. The thermodynamic parameters of the binding process were determined. The binding to DNA, as one of the main pathways in the cell death cycle, was analyzed by molecular docking. The cytotoxicity was determined towards HCT116, A375, MCF-7, and A2780 cell lines. The most active compound was Cu-PLAG due to the presence of PLAG and two thiocyanate ligands.
吡啶醛缩氨基胍（PLAG）及其过渡金属配合物是具有有趣性质的生物活性化合物。在本贡献中，合成了三种新的金属-PLAG 配合物，Zn(PLAG)(SO)(HO)]·HO（Zn-PLAG）、[Co(PLAG)]SO·2HO（Co-PLAG）和[Fe(PLAG)]SO·2HO（Fe-PLAG），并通过 X 射线晶体学进行了表征。通过 Hirshfeld 表面分析比较了控制晶体结构稳定性的分子间相互作用与 Cu(PLAG)(NCS)（Cu-PLAG）的相互作用。在 B3LYP/6-31+G(d,p)(H,C,N,O,S)/LanL2DZ（Fe，Co，Zn，Cu）上优化了结构，并通过自然键轨道理论和分子中的原子量子理论评估了稳定性。特别强调了研究配体的稳定性和反应性。通过荧光光谱滴定法研究了这些化合物与牛血清白蛋白和人血清白蛋白的结合。显示了配合物的几何形状和各种配体对蛋白质结合的重要性。这些结果通过分子对接研究得到了补充，以阐明最重要的相互作用。确定了结合过程的热力学参数。通过分子对接分析了与 DNA 的结合，DNA 是细胞死亡周期的主要途径之一。测定了对 HCT116、A375、MCF-7 和 A2780 细胞系的细胞毒性。最活跃的化合物是 Cu-PLAG，因为它含有 PLAG 和两个硫氰酸根配体。
