University of Tunis El Manar, Faculty of Sciences of Tunis, Laboratory of Materials, Crystal Chemistry and Applied Thermodynamics (LR15ES01), 2092 El Manar II, Tunis, Tunisia.
University of Tunis El Manar, Laboratory of Biomolecules, Venoms and Theranostic Applications (LR20IPT01), Pasteur Institute of Tunis, Tunis, Tunisia.
J Inorg Biochem. 2024 Nov;260:112672. doi: 10.1016/j.jinorgbio.2024.112672. Epub 2024 Jul 25.
Melanoma is a skin cancer that arises from melanocytes and can spread quickly to the other organs of the body, if not treated early. Generally, melanoma shows an inherent resistance to conventional therapies. In this regard, new potential drugs are being developed as possible treatments for melanoma. In this paper, we report the synthesis of a new decavanadate compound with organic molecules for a potential therapeutic application. The tetra-[methylimidazolium] dihydrogen decavanadate(V) salt (CHN)[HVO] is characterized by single-crystal X-ray diffraction, by FT-IR, UV-Vis and V NMR spectroscopy, as well as by thermal analysis (TGA and DSC). The compound crystallizes in the monoclinic centrosymmetric space group P2/c. Its formula unit consists of one dihydrogen decavanadate anion [HVO] and four organic 4-methylimidazolium cations (CHN). Important intermolecular interactions are N-H···O and O-H···O hydrogen bonds and π-π stacking interactions between the organic cations, revealed by analysis of the Hirshfeld surface and its two-dimensional fingerprint plots. Interestingly, this compound inhibits the viability of IGR39 cells with IC values of 14.65 μM and 4 μM after 24 h and 72 h of treatment, respectively. The analysis of its effect by flow cytometry using an Annexin V-FITC/IP cell labeling, showed that (CHN)HVO compound induced IGR39 cell apoptosis and necrosis. Molecular docking studies performed against TNFR1 and GPR40, as putative targets, suggest that the (CHN)[HVO] compound may act as inhibitor of these proteins, known to be overexpressed in melanoma cells. Therefore, we could consider it as a new potential metallodrug against melanoma.
黑色素瘤是一种起源于黑色素细胞的皮肤癌,如果不早期治疗,它可能会迅速扩散到身体的其他器官。一般来说,黑色素瘤对传统疗法表现出固有抗性。在这方面,新的潜在药物正在被开发为治疗黑色素瘤的可能方法。在本文中,我们报告了一种新的含有机分子的十钒酸盐化合物的合成,用于潜在的治疗应用。四-[甲基咪唑鎓]二氢十钒酸盐(V)盐(CHN)[HVO]通过单晶 X 射线衍射、FT-IR、UV-Vis 和 V NMR 光谱以及热分析(TGA 和 DSC)进行了表征。该化合物在中心对称的单斜 P2/c 空间群中结晶。其分子式单元由一个二氢十钒酸根阴离子[HVO]和四个有机 4-甲基咪唑鎓阳离子(CHN)组成。通过分析 Hirshfeld 表面及其二维指纹图,揭示了重要的分子间相互作用,包括 N-H···O 和 O-H···O 氢键以及有机阳离子之间的π-π堆积相互作用。有趣的是,该化合物在 24 小时和 72 小时的治疗后,对 IGR39 细胞的抑制活性分别为 14.65 μM 和 4 μM。通过用 Annexin V-FITC/PI 细胞标记物进行流式细胞术分析其作用,表明(CHN)HVO 化合物诱导 IGR39 细胞凋亡和坏死。针对 TNFR1 和 GPR40 这两个假定靶点进行的分子对接研究表明,(CHN)[HVO]化合物可能作为这些蛋白的抑制剂发挥作用,已知这些蛋白在黑色素瘤细胞中过度表达。因此,我们可以将其视为一种针对黑色素瘤的新型潜在金属药物。