G Prakasha, Revanasiddappa H D, B Jayalakshmi, T Prabhakar B, Shivamallu Chandan, Viswanath Prashant M, Achar Raghu Ram, Silina Ekaterina, Stupin Victor, Manturova Natalia, Shati Ali A, Alfaifi Mohammad Y, Elbehairi Serag Eldin I, Armaković Sanja J, Armaković Stevan, Kollur Shiva Prasad
Department of Studies in Chemistry, University of Mysore, Manasagangotri, Mysuru 570 006, Karnataka, India.
Department of Botany, Government College for Women, Mandya 571 401, Karnataka, India.
Pharmaceuticals (Basel). 2023 Jan 13;16(1):125. doi: 10.3390/ph16010125.
The emerging interest in the field of coordination chemistry and their biological applications has created a novel impact in the field of chemical biology. With this motivation, in this work we have synthesized a novel benzimidazole derived imine ligand, 2-((E)-((1H-benzo[d]-2-yl)methylimino)methyl)-4-fluorophenol () and its Co(III) and Cu(II) complexes. The metal complexes (-) were synthesized in 2:1 (: metal ion) and 1:1:1 (: metal ion: 1,10-phen) ratios. Structural elucidations of all the synthesized compounds were performed using FT-IR, UV-Visible, NMR, Mass spectroscopy and elemental analysis techniques. A combination of first principles calculations and molecular dynamics simulations was applied to computationally investigate the structural, reactive, and spectroscopic properties of the newly synthesized ligand and its complexes with copper and cobalt metal ions. Quantum-mechanical calculations in this study were based on the density functional theory (DFT), while molecular dynamics (MD) simulations were based on the OPLS4 force field. The DFT calculations were used to obtain the reactive and spectroscopic properties of the ligand and its complexes, while molecular dynamics (MD) simulations were used to address the ligand's reactivity with water. Further, the in vitro anti-proliferative activity of the compounds was tested against the A549, Ehrlich-Lettre ascites carcinoma (EAC), SIHA and NIH3T3 cell lines. The biological results depicted that the compound , with molecular formula CHClCoFNO exhibited profound anti-proliferative activity against the EAC cell line with a significant IC value of 10 µm when compared to its parent ligand and other remaining metal complexes under study. Various assays of hematological parameters (alkaline phosphate, creatinine, urea, RBC and WBC) were performed, and significant results were obtained from the experiments. Furthermore, the effect of on neovascularization was evaluated by stimulating the angiogenesis with rVEGF, which was compared with non-tumor models. The EAC cells were cultured in vivo and administrated with 50 and 75 mg/kg of two doses and tumor parameters were evaluated.
配位化学领域及其生物应用方面日益增长的兴趣在化学生物学领域产生了新的影响。出于这一动机，在本工作中，我们合成了一种新型的苯并咪唑衍生的亚胺配体，2-((E)-((1H-苯并[d]-2-基)甲基亚氨基)甲基)-4-氟苯酚（）及其钴(III)和铜(II)配合物。金属配合物（-）以2:1（:金属离子）和1:1:1（:金属离子:1,10-菲咯啉）的比例合成。使用傅里叶变换红外光谱、紫外可见光谱、核磁共振、质谱和元素分析技术对所有合成化合物进行结构解析。结合第一性原理计算和分子动力学模拟，对新合成的配体及其与铜和钴金属离子的配合物的结构、反应性和光谱性质进行了计算研究。本研究中的量子力学计算基于密度泛函理论（DFT），而分子动力学（MD）模拟基于OPLS4力场。DFT计算用于获得配体及其配合物的反应性和光谱性质，而分子动力学（MD）模拟用于研究配体与水的反应性。此外，测试了这些化合物对A549、艾氏腹水癌（EAC）、SiHa和NIH3T3细胞系的体外抗增殖活性。生物学结果表明，分子式为CHClCoFNO的化合物对EAC细胞系表现出显著的抗增殖活性，与母体配体和其他研究中的金属配合物相比，其IC值为10 µm，具有显著性。进行了各种血液学参数（碱性磷酸酶、肌酐、尿素、红细胞和白细胞）测定，并从实验中获得了显著结果。此外，通过用rVEGF刺激血管生成来评估对新血管形成的影响，并与非肿瘤模型进行比较。将EAC细胞在体内培养，给予50和75 mg/kg两种剂量，并评估肿瘤参数。
