Photocytotoxic and anaerobic DNA cleavage activity of binuclear 3,3′-dithiodipropionic acid cobalt(II) complexes having phenanthroline bases |
| |
Authors: | Debojyoti Lahiri Tuhin Bhowmick Bhabatosh Banik Reema Railkar Suryanarayanarao Ramakumar Rajan R. Dighe Akhil R. Chakravarty |
| |
Affiliation: | 1. Department of Inorganic and Physical Chemistry, Indian Institute of Science, Sir C.V. Raman Avenue, Bangalore 560 012, India;2. Department of Physics and Bioinformatics Center, Indian Institute of Science, Sir C.V. Raman Avenue, Bangalore 560 012, India;3. Department of Molecular Reproduction, Development and Genetics, Indian Institute of Science, Sir C.V. Raman Avenue, Bangalore 560 012, India |
| |
Abstract: | Dicobalt(II) complexes [{(B)CoII}2(μ-dtdp)2] (1–3) of 3,3′-dithiodipropionic acid (dtdp) and phenanthroline bases (B), viz. 1,10-phenanthroline (phen in 1), dipyrido[3,2-d:2′,3′-f]quinoxaline (dpq in 2) and dipyrido[3,2-a:2′,3′-c]phenazine (dppz in 3), have been prepared, characterized and their photo-induced anaerobic DNA cleavage activity studied. The elemental analysis and mass spectral data suggest binuclear formulation of the complexes. The redox inactive complexes have magnetically non-interacting dicobalt(II) core showing magnetic moment of ∼3.9 μB per cobalt(II) center. The complexes show good binding propensity to calf thymus DNA giving Kb values within 4.3 × 105–4.0 × 106 M−1. Thermal melting and viscosity data predict DNA groove binding and/or partial intercalative nature of the complexes. The complexes show significant anaerobic DNA cleavage activity in green light under argon atmosphere possibly involving radical species generated from the disulfide moiety in a type-I pathway. The DNA cleavage reaction under aerobic medium in green light is found to involve hydroxyl radical species. The dppz complex 3 exhibits significant photocytotoxicity in HeLa cervical cancer cells with an IC50 value of 2.3 μM in UV-A light of 365 nm, while it is essentially non-toxic in dark giving an IC50 value of >200 μM. A significant reduction of the dark toxicity of the organic dppz base (IC50 = 8.3 μM in dark) is observed on binding to the cobalt(II) center while essentially retaining its photocytotoxicity in UV-A light (IC50 = 0.4 μM). |
| |
Keywords: | CT, calf thymus dppz, dipyridophenazine dpq, dipyridoquinoxaline DMF, dimethylformamide DMSO, dimethyl sulfoxide EB, ethidium bromide Dtdp, 3,3&prime -dithiodipropionic acid MPA, 3-mercaptopropionic acid NC, nicked circular PDT, photodynamic therapy phen, 1,10-phenanthroline SC, supercoiled SOD, superoxide dismutase TAE, tris-acetate&ndash EDTA TBAP, tetrabutylammonium perchlorate Tris, tris(hydroxymethyl)aminomethane TEMP, 2,2,6,6-tetramethyl-4-piperidone DABCO, 1,4-diazabicyclo[2.2.2]octan |
本文献已被 ScienceDirect 等数据库收录! |
|