RESUMO
A new mononuclear Zn(II) complex, trans-[Zn(Pir)2(DMSO)2], where Pir(-) is 4-hydroxy-2-methyl-N-2-pyridyl-2H-1,2-benzothiazine-3-carboxamide-1,1-dioxide (piroxicam), has been synthesized and characterized. The crystal structure of the complex was obtained by the single crystal X-ray diffraction technique. The interaction of the complex with DNA and BSA was investigated. The complex interacts with FS-DNA by two binding modes, viz., electrostatic and groove binding (major and minor). The microenvironment and the secondary structure of BSA are changed in the presence of the complex. The anticancer effects of the seven complexes of oxicam family were also determined on the human K562 cell lines and the results showed reasonable cytotoxicities. The interactions of the oxicam complexes with BSA and DNA were modeled by molecular docking and molecular dynamic simulation methods.
Assuntos
Complexos de Coordenação/química , Complexos de Coordenação/toxicidade , DNA/metabolismo , Modelos Moleculares , Piroxicam/toxicidade , Soroalbumina Bovina/metabolismo , Zinco/farmacologia , Animais , Sítios de Ligação , Ligação Competitiva , Bovinos , Complexos de Coordenação/metabolismo , Cristalografia por Raios X , Dimetil Sulfóxido/química , Elétrons , Transferência de Energia , Humanos , Concentração Inibidora 50 , Células K562 , Cinética , Conformação Molecular , Simulação de Acoplamento Molecular , Piroxicam/química , Piroxicam/metabolismo , Ligação Proteica , Espectrometria de Fluorescência , Espectrofotometria Ultravioleta , Triptofano/metabolismoRESUMO
A mononuclear Ru(II) complex containing two piroxicam (Pir(-)) ligands was synthesized and fully characterized. Interaction studies of the Pir(-) anion and the Ru(II) complex with DNA and BSA were carried out using spectroscopic techniques. The results suggested that the Pir(-) anion binds to DNA in a moderately strong fashion via intercalation between the base stacks of double-stranded DNA, while the Ru(II) complex is a groove binder and interacts with DNA with more affinity. Moreover, the results demonstrated that the microenvironment and the secondary structure of BSA were changed in the presence of Pir(â¾) and Ru(II) complex. The free Pir(â¾) ligand and the Ru(II) complex can lead to the photocleavage of DNA supercoiled pUC57. Finally, the binding of the Ru(II) complex to BSA and DNA was modeled by molecular docking and molecular dynamic simulation methods.