Paolillo Maddalena, Ferraro Giarita, Sahu Gurunath, Pattanayak Pratikshya Das, Garribba Eugenio, Halder Sourangshu, Ghosh Riya, Mondal Bipul, Chatterjee Pabitra B, Dinda Rupam, Merlino Antonello
Department of Chemical Sciences, University of Naples Federico II, Complesso Universitario di Monte Sant'Angelo, Via Cintia, I-80126 Napoli, Italy.
Department of Chemistry, National Institute of Technology, Rourkela 769008, Odisha, India.
J Inorg Biochem. 2025 Mar;264:112787. doi: 10.1016/j.jinorgbio.2024.112787. Epub 2024 Nov 29.
Vanadium compounds (VCs) exhibit a broad range of pharmacological properties, with their most significant medical applications being in the treatment of cancer and diabetes. The therapeutic effects and mode of action of VCs may be associated with their ability to bind proteins and, consequently, understanding the VC-protein interaction is of paramount importance. Among the promising VCs, the VO complex with the aroylhydrazone furan-2-carboxylic acid ((3-ethoxy-2-hydroxybenzylidene)hydrazide, hereafter denoted as VC1), deserves attention, since it exhibits cytotoxicity against various cancer cell lines, including HeLa. The interaction between VC1 and its analogue, denoted as VC2 (the dioxidovanadium(V) complex with (E)-N'-(1-(2-hydroxy-5-methoxyphenyl)ethylidene)furan-2-carbohydrazide), and hen egg white lysozyme (HEWL) was examined by UV-vis spectroscopy, fluorescence, circular dichroism, and X-ray crystallography. The interaction of VC1 and VC2 with HEWL does not alter the protein secondary and tertiary structure. Crystallographic studies indicate that the two metal complexes or V-containing fragments originating from VC1 and VC2 bind the protein via non-covalent interactions. Furthermore, when bound to HEWL, two VC1 molecules and two VC2 molecules form a supramolecular association stabilized by stacking interactions. This type of interaction could favour the binding of similar compounds to proteins and affect their biological activity.
钒化合物（VCs）具有广泛的药理特性，其最重要的医学应用是治疗癌症和糖尿病。VCs的治疗效果和作用方式可能与其结合蛋白质的能力有关，因此，了解VC-蛋白质相互作用至关重要。在有前景的VCs中，与呋喃-2-羧酸芳酰腙形成的VO配合物（（3-乙氧基-2-羟基苄叉）酰肼，以下简称VC1）值得关注，因为它对包括HeLa在内的多种癌细胞系具有细胞毒性。通过紫外可见光谱、荧光、圆二色性和X射线晶体学研究了VC1及其类似物（称为VC2，即与（E）-N'-（1-（2-羟基-5-甲氧基苯基）亚乙基）呋喃-2-碳酰肼形成的二氧化钒（V）配合物）与鸡蛋清溶菌酶（HEWL）之间的相互作用。VC1和VC2与HEWL的相互作用不会改变蛋白质的二级和三级结构。晶体学研究表明，源自VC1和VC2的两种金属配合物或含钒片段通过非共价相互作用与蛋白质结合。此外，当与HEWL结合时，两个VC1分子和两个VC2分子通过堆积相互作用形成超分子缔合。这种相互作用类型可能有利于类似化合物与蛋白质的结合并影响其生物活性。
