Molecular docking and Multi-spectroscopic studies on the intraction calf thymus DNA with the drug ketotifen fumarate

The interaction of ketotifen fumarate with calf thymus DNA (CT-DNA) at physiological pH has been investigated by absorption, emission, circular dichroism, viscosity studies, and molecular modeling. Spectrophotometric studies of the interaction of ketotifen with DNA have shown that it can binds to CT-DNA and the DNA binding constant (Kb =5.79 ×104 M-1) is comparable to groove binding drugs. fluorimetric studies with hoechst 33258 have shown that ketotifen fumarate exhibit the ability to displace the DNA-bound hoechst 33258 indicating that it binds to DNA in strong competition with Hoechst 33258 for the groove binding. Thermodynamic parameters (ΔH < 0 and ΔS < 0) indicatedthat hydrogen bond and van der Waals play main roles in the binding of ketotifen to CT-DNA. Circular dichroism spectroscopy (CD) was employed to measure the conformational change of CT-DNA in the presence of ketotifen fumarate, which verified the groove binding mode. Furthermore, the drug induces detectable changes in its viscosity. The molecular modeling results illustrated that ketotifen strongly binds to groove of DNA.

کلیدواژه ها:

ketotifen fumarate ، DNA interaction ، Molecular docking ، Groove binding