DNA binding studies of novel Copper(II) complexes containing L-tryptophan as chiral auxiliary: in vitro antitumor activity of Cu-Sn2 complex in human neuroblastoma cells.
Novel trinuclear complexes C23H31N6O6CuSn2Cl5 [1], C23H31N6O6CuZr2Cl5 [2], C23H31N6O6ZnSn2Cl5 [3], and C23H31N6O6ZnZr2Cl5 [4] were synthesized and characterized by spectroscopic (IR, 1H, 13C, 2D COSY, and 119Sn NMR, EPR, UV-vis, ESI-MS) and analytical methods. In complexes 1-4, the geometry of copper and zinc metal ions were described as square-based pyramidal with l-tryptophan coordinated to copper/zinc via carboxylate group while Sn/Zr was present in the hexacoordinate environment. The interaction of 1 and 2 with calf thymus DNA in Tris buffer was studied by electronic absorption titration, luminescence titration, cyclic voltammetry, circular dichroism, and viscometric measurements. The emission quenching of these complexes by [Fe(CN)6]4- depressed greatly when bound to DNA. Observed changes in the circular dichoric spectra of DNA in presence of 1 and 2 support the strong binding of complexes with DNA. The relative specific viscosity of DNA bound to 1 and 2 decreased, indicating that the complexes bind to DNA via covalent binding. The results reveal that the extent of DNA binding of 1 was greater than that of 2. To evaluate the mechanistic pathway of DNA inhibition, counting experiments and MTT assay were employed to assess the induction of apoptosis by 1. Western blot analysis of whole cell lysates and mitochondrial fractions with Bcl-2 and p-53 family proteins and caspase-3 colorimetry assay were also carried out on a human neuroblastoma cell line SY5Y.
Chauhan
Mala
M
Department of Chemistry, Aligarh Muslim University, Aligarh-202002, India, and National Institute of Immunology, New Delhi, India.
Banerjee
Kakoli
K
Arjmand
Farukh
F
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001665:Binding Sites; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003300:Copper / Q000737:chemistry*; D004247:DNA / Q000737:chemistry* / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D004578:Electron Spin Resonance Spectroscopy / Q000379:methods; D006801:Humans; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D015394:Molecular Structure; D009447:Neuroblastoma / Q000188:drug therapy* / Q000378:metabolism; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D012680:Sensitivity and Specificity; D013055:Spectrophotometry, Infrared / Q000379:methods; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014001:Tin / Q000737:chemistry*; D017186:Titrimetry; D014364:Tryptophan / Q000737:chemistry*; D014783:Viscosity; D015032:Zinc / Q000737:chemistry; D015040:Zirconium / Q000737:chemistry
D000970:Antineoplastic Agents; D009942:Organometallic Compounds; D014001:Tin; D003300:Copper; D014364:Tryptophan; D004247:DNA; D015040:Zirconium; D053148:Caspase 3; D015032:Zinc