Luo, Mei, Zhang, Jing-Cheng, Yin, Hao, Wang, Cheng-Ming, Xie, Lan, Li, Kang-Po, Goto, Masuo, Morris-Natschke, Susan L., Lee, Kuo-Hsiung, Zhang, Jia-Hai, Zhang, Yan-Min, and Zhang, Xue-Ru
Six new Pd(II), Pt(II) and Ag(I) complexes, (1);{Pd (L 1)]2C 6 H 4 } 2 Cl 4 } (2); Pt(L 2)(DMSO)Cl; 3; {PtL 5 ] 2 C 6 H 4 } 2 ·PhCOO-⋅11NO 3 -; 4; {[Pt(L 4)] 2 C 6 H 4 }; the binuclear cyclometalated complex the polymer chain (5); {[PtL 5 ]C 6 H 4 }·NO 3 -}; and the polymeric silver species (6); Zn(L 6) 2 ·AgNO 3 ·CHCl 3 were synthesized and thoroughly characterized using X-ray diffraction and spectroscopic techniques (L 1 =(S,S)-1,4-i-PrOx] 2 C 6 H 4 } 2 Cl 4 , L 2 =Di(2,2-bis(4R-isopropyl-4,5-dihydro-oxazol-2-yl)acetonitrile) zinc (II) (B R1);L 3 = 1,4-bis(4R-benzyl-4,5-dihydro-oxazol-2-yl)benzene (A R2); L 4 = 1,4-bis(4R-benzyl-4,5-dihydro-oxazol-2-yl)benzene,L 5 =1,4-bis(4R-benzyl-4,5-dihydro-oxazol-2-yl)-benzene,L 6 =Di(2,2-bis(4S-isopropyl-4,5-dihydrooxazol-2-yl)acetonitrile) zinc (II). Complexes 1-6 showed cytotoxic effects against human tumour cell lines, including a multidrug-resistant subline. Oxazoline and Pd complex 1 induced apoptosis in A549 cells. DFT calculations were also performed to exhibit the excellent bioactivity of complex 1 against A549, MDA-MB-231, and KB cells. Complex 1, with the best docking score and a stable interaction network within the binding site of the G-quadruplex, could stably interact with the G-quadruplex. Additionally, complex 1 was further used in the animal experiment of human lung adenocarcinoma cells in nude mice. By comparing with the model control group, the tumour volume, relative tumour volume and relative tumour proliferation rate T/C decreased significantly in the cisplatin group and compound 1 (complex 1) group. [Display omitted] • Six novel mononuclear, dinuclear and one-dimensional Pd(II), Pt(II) and Ag(I) complexes related with oxazoline ligands have been easily prepared in good yields from 68% to 92%. • Pd(II), Pt(II) and Ag(I) complexes showed different cytotoxic effects against human tumour cell lines, especially complex 1 could induce an apoptosis in cell A549. • DFT calculations and molecular docking simulations were performed to explore the possible interaction mechanism between these complexes and the binding pocket of G-quadruplex. • Comparing with the control group, the tumour volume, relative tumour volume and relative tumour proliferation rate T/C decreased significantly in the animal experiment by using complex 1. [ABSTRACT FROM AUTHOR]