Justin Dhanaraj Chellaian, Johnson Jijo
Department of Chemistry, University College of Engineering, (Anna University Constituent College), Nagercoil - 629004, Tamil Nadu, India.
Department of Chemistry, University College of Engineering, (Anna University Constituent College), Nagercoil - 629004, Tamil Nadu, India.
Mater Sci Eng C Mater Biol Appl. 2017 Sep 1;78:1006-1015. doi: 10.1016/j.msec.2017.04.152. Epub 2017 Apr 27.
A tridentate ONO donor bishydrazone ligand, 3-(((3-oxoindolin-2-ylidene)hydrazono) methyl)quinoxalin-2(1H)-one (L) was synthesized. Using the ligand, mononuclear metal complexes of the type [M(L)(OAc)] (M=Co(II), Ni(II), Cu(II) and Zn(II), OAc=-OCOCH) were synthesized. The newly synthesized compounds were thoroughly characterized by various analytical and spectral techniques. Tetrahedral geometry was proposed for Co(II), Ni(II) and Zn(II) complexes, while square planar geometry has been assigned to the Cu(II) complex. The in vitro antibacterial, antifungal and antioxidant studies reveal that the Cu(II) complex of the bishydrazone ligand possess higher activities. DNA binding studies suggest that the present compounds interact with CT DNA through intercalation. This was further supported by molecular docking. Gel electrophoresis studies substantiated the involvement of free radicals in the cleavage of pUC18 DNA. In vitro cytotoxicity of the compounds against MCF-7 cell line was also examined. The molecular modeling studies reveal that the compounds strongly interact with VEGFR-2 kinase receptor through hydrogen bonding, π-π, π-cation and sigma-π interactions. The bioavailability and bioactivity determination of the compounds suggest that the present compounds may be utilized as drug candidates.
合成了一种三齿ONO供体双腙配体,即3 -(((3 - 氧代吲哚啉 - 2 - 亚基)腙基)甲基)喹喔啉 - 2(1H)-酮(L)。使用该配体合成了[M(L)(OAc)]类型的单核金属配合物(M = Co(II)、Ni(II)、Cu(II)和Zn(II),OAc = -OCOCH₃)。通过各种分析和光谱技术对新合成的化合物进行了全面表征。推测Co(II)、Ni(II)和Zn(II)配合物具有四面体几何构型,而Cu(II)配合物具有平面正方形几何构型。体外抗菌、抗真菌和抗氧化研究表明,双腙配体的Cu(II)配合物具有更高的活性。DNA结合研究表明,本化合物通过插入作用与CT DNA相互作用。分子对接进一步支持了这一点。凝胶电泳研究证实了自由基参与了pUC18 DNA的切割。还检测了化合物对MCF - 7细胞系的体外细胞毒性。分子模拟研究表明,化合物通过氢键、π - π、π - 阳离子和σ - π相互作用与VEGFR - 2激酶受体强烈相互作用。化合物的生物利用度和生物活性测定表明,本化合物可作为候选药物。