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Transition metal complexes of 6‐mercaptopurine: Characterization, Theoretical calculation, DNA‐Binding, molecular docking, and anticancer activity
Applied Organometallic Chemistry ( IF 3.9 ) Pub Date : 2020-11-03 , DOI: 10.1002/aoc.6041
Abeer A. Sharfalddin 1 , Abdul‐Hamid Emwas 2 , Mariusz Jaremko 3 , Mostafa A. Hussien 1, 4
Affiliation  

6‐mercaptopurine (6‐MP) is used for treating various cancers and autoimmune disorders. A few examples of transition metal complexes of 6‐MP have been shown to enhance its anticancer activity, but many remain untested. We isolated five highly stable and colored metal complexes of 6‐MP and confirmed their structures by elemental analysis, spectral, and thermal techniques. Infrared (IR) spectra revealed that 6‐MP is a bidentate ligand that interacts through sulfur and pyrimidine nitrogen in a 1:2 (M:L) molar ratio. The magnetic susceptibility and electron paramagnetic resonance (EPR) spectra for the Cu(II) complex revealed an octahedral arrangement around the metal ion with strong covalent bonding. The fully optimized geometries of the metal structures obtained using density function theory (DFT)/B3LYP calculations were used to verify the structural and biological features. DNA titration revealed that the octahedral Cu(II) complex has a critical binding constant value of Kb = 8 × 105. Docking studies using three different cancer protein receptors were used to predict the biological applications of the synthesized drug‐metal complexes. Finally, cytotoxicity assays against a myeloma cancer cell line (MM) and a colon cancer cell line (Caco‐2) revealed favorable anticancer activity for the copper complex, exceeding that of the gold‐standard chemotherapeutic cisplatin.

中文翻译:

6-巯基嘌呤的过渡金属配合物:表征,理论计算,DNA结合,分子对接和抗癌活性

6-巯基嘌呤(6-MP)用于治疗各种癌症和自身免疫性疾病。已经显示了一些6-MP过渡金属配合物的实例可以增强其抗癌活性,但许多未经测试。我们分离了5种6-MP高度稳定且有色的金属配合物,并通过元素分析,光谱和热技术证实了它们的结构。红外(IR)光谱表明,6-MP是一种二齿配体,它以1:2(M:L)的摩尔比通过硫和嘧啶氮相互作用。Cu(II)配合物的磁化率和电子顺磁共振(EPR)光谱显示金属离子周围具有强共价键的八面体排列。使用密度函数理论(DFT)/ B3LYP计算获得的金属结构的完全优化几何形状用于验证结构和生物学特征。DNA滴定显示八面体Cu(II)络合物的临界结合常数为K b = 8×105。使用三种不同的癌蛋白受体的对接研究用于预测合成的药物金属配合物的生物学应用。最后,针对骨髓瘤癌细胞系(MM)和结肠癌细胞系(Caco-2)的细胞毒性试验显示,铜配合物具有良好的抗癌活性,超过了金标准化疗顺铂的抗癌活性。
更新日期:2020-12-22
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