EXPERIMENTAL AND COMPUTATIONAL STUDY OF BINDING INTERACTION OF ALKOXY DERIVATIVES OF N-ARYLHYDROXAMIC ACIDS WITH DNA
Objective: Â Binding affinity towards DNA for small molecules is very important in the development of new therapeutic reagents. Interaction between N-Arylhydroxamic acid derivatives N-p-Tolyl-4-Ethoxybenzohydroxamic acid (p-TEBHA) and N-o- Tolyl-4-Ethoxybenzohydroxamic Acid (o-TEBHA), with calf thymus DNA (CT DNA) were studied by UVâ€“visible absorption, fluorescence, Â viscosity measurement and molecular docking.
Methods: Â The absorption and emission spectra of DMSO solution of hydroxamic acid derivatives were studied for their binding activity with calf-thymus DNA by titration with increasing amount hydroxamic acids. Docking was performed by HEX software.
Results: Â Fluorescent spectra showed that CT DNA quenches the emission spectra of p-TEBHA & o-TEBHA with binding constant 1.6 Ñ… 108 M-1 and 4.3 Ñ… 103 M-1 respectively. Competitive study with ethidium bromide (EB) indicates that p-TEBHA can displace the DNA-bound EB suggesting strong competition with EB whereas o-TEBHA does not displace the DNA-bounded Ethidium bromide effectively. UV study of the interaction of the complexes with calf-thymus DNA has shown that the hydroxamic acid derivatives can bind with CT DNA. The docking studies were used to predict the mode of interaction of the drug with DNA. It was observed that as far as binding strength was concerned the computational results complemented the experimental results.
Conclusion: Â Investigated hydroxamic acid derivatives are found to be strong DNA binders and seem to have promising drug like nature.
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