DNA-binding, cleavage, antibacterial and in vitro anticancer activity of copper(II) mixed ligand complexes of 2-(((6-chloro-1H-benzo[d]imidazol-2-yl)methyl)amino)aceticacid and polypyridyl ligands.

A tridentate ligand(A), 2-(((6-chloro-1H-benzo[d]imidazol-2-yl)methyl)amino) aceticacid (Cl-BIGH) was synthesised by the Phillips condensation of 4-chlorobenzene-1,2-diamine and iminodiaceticacid in 1:2 molar ratio. Its Cu(II) mixed ligand complexes[Cu(II)-A-L] were obtained by involving other co-ligands(L): 2,2΄-bipyridine(L1), 4,4΄-dimethyl-2,2΄-bipyridyl(L2), 5,5΄-dimethyl-2,2΄-bipyridyl(L3) and 1,10 phenanthroline(L4). The complexes were characterized by elemental analysis, thermal analysis, molar conductance, magnetic moment measurements, X-ray diffraction, FTIR, UV-Visible, ESR spectroscopy, mass spectrometry and cyclic voltammetry. From the spectral and analytical data, the ternary complexes [Cu(Cl-BIGH)(L1-4)]ClO4 were found to form in 1:1:1(Cu(II): Cl-BIGH: L) molar ratio. The geometry of the mixed-ligand complexes were found to be 5-coordinated square pyramidal or trigonal bipyramidal with polycrystalline natures. The DNA binding and cleaving abilities, antibacterial and the in vitro cytotoxicity of the complexes were explored. The molecular docking was used to predict the efficiency of binding of the metal complexes with COX- 2.Communicated by Ramaswamy H. Sarma.

Structural investigation, DNA interactions and in vitro anticancer studies of transition metal complexes of 3-(2-(2, 4-dihydroxy benzylidene) hydrazinyl) quinoxalin-2(1H) -one.

The Schiff base ligand, 3-(2-(2, 4-dihydroxybenzylidene) hydrazinyl) quinoxalin-2(1H)-one (RHQO) has been synthesized and characterized by spectral and single crystal X-ray analysis. The Mn(II), Ni(II) and Cu(II) complexes of RHQO have been synthesized and characterized by FT-IR, UV-VIS, mass, EPR spectra, CHN, thermo gravimetric analysis, magnetic susceptibility and conductivity measurements. The morphology of the ligand and complexes is studied by Scanning Electron Microscopy. The metal complexes formed were found to be polymeric in nature. The abilities of the ligand and its metal complexes to interact and bind with calf thymus DNA (CT-DNA) has been studied by electronic absorption spectroscopy and their quantitative binding strength was evaluated in terms of their intrinsic binding constant (Kb). The cleavage interaction of the ligand and its metal complexes with super coiled pBR 322 DNA has been investigated by agarose gel electrophoresis. Cytotoxicity of the Cu(II) and Ni(II) complexes was evaluated using various cancer cell lines, Human cervical cancer cell line (Hela), B16 melanoma F10(B16-F10), Human ovarian cancer cell (SKOV3) and Breast cancer cell line (MCF7) by MTT assay. The results indicated that the ligand and its metal complexes bind with CT-DNA by groove binding mode and cleaved the supercoiled pBR 322 DNA in to nicked form. The Ni(II) and Cu(II) complexes exhibited anticancer activity without affecting the normal CHO-K1 cell lines. Communicated by Vsevolod Makeev.

Indole and 2,4-Thiazolidinedione conjugates as potential anticancer modulators.

BACKGROUND: Thiazolidinediones (TZDs), also called glitazones, are five-membered carbon ring molecules commonly used for the management of insulin resistance and type 2 diabetes. Recently, many prospective studies have also documented the impact of these compounds as anti-proliferative agents, though several negative side effects such as hepatotoxicity, water retention and cardiac issues have been reported. In this work, we synthesized twenty-six new TZD analogues where the thiazolidinone moiety is directly connected to an N-heterocyclic ring in order to lower their toxic effects. METHODS: By adopting a widely applicable synthetic method, twenty-six TZD derivatives were synthesized and tested for their antiproliferative activity in MTT and Wound healing assays with PC3 (prostate cancer) and MCF-7 (breast cancer) cells. RESULTS: Three compounds, out of twenty-six, significantly decreased cellular viability and migration, and these effects were even more pronounced when compared with rosiglitazone, a well-known member of the TZD class of antidiabetic agents. As revealed by Western blot analysis, part of this antiproliferative effect was supported by apoptosis studies evaluating BCL-xL and C-PARP protein expression. CONCLUSION: Our data highlight the promising potential of these TZD derivatives as anti-proliferative agents for the treatment of prostate and breast cancer.