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Exploring the DNA binding efficacy of Cobalt(II) and Copper(II) complexes of hydroxamic acids and explicating their anti-cancer propensity

Thakur, Yamini; Agrawal, Rainy; Tripathi, Mamta; Siddiqi, Mohammad Khursheed; Mohapatra, Eli; Khan, Rizwan Hasan; Pande, Rama*
Science Citation Index Expanded
河北医科大学

摘要

Calf-thymus DNA (ct-DNA) binding efficacy of Bis(N-p-tolylbenzohydroxamato)Cobalt(II), [N-p-TBHACo(II)] and Bis(N-p-naphthylbenzohydroxamato)Copper(II), [N-p-NBHA-Cu(II)] have been studied by multi-spectroscopic approaches coupled with viscosity measurements and molecular docking. The binding constants of the complexes towards ct-DNA evaluated are 1.68 /- 0.03 x 10(5) M-1 and 1.52 /- 0.07 x 10(5) M-1 for N-p-TBHA-Co(II) and N-p-NBHA-Cu(II), respectively. Stern-Volmer quenching constants were also evaluated from fluorescence measurement. The mode of binding was further disclosed by ethidium bromide and Hoechst 33258 displacement, confirmed by fluorescence measurement, which reveals a groove mode of binding. The three-dimensional fluorescence spectroscopy was also applied to know the interaction between complexes and ct-DNA. The relative viscosity increases with increase in the concentration of the N-p-TBHA-Co(II) and N-p-NBHA-Cu(II) while adding to ct-DNA was also uncovered, but lesser than the ct-DNA alone suggesting groove binding mode. DRS-FTIR analysis, cyclic voltammetry and circular dichroism studies further confirmed a strong interaction between complexes and ct-DNA. The docked posture of ct-DNA with N-p-TBHA-Co(II) and N-p-NBHA-Cu(II) uncover the strong binding interactions which revealed minor groove binding. The in-vitro cytotoxicity studies was carried out by MIT assay for both the complexes against MCF-7 breast cancer cell line.

关键词

ct-DNA Hydroxamic acid-Metal complexes Binding Stern-volmer constants MCF-7 breast cancer cell line