Synthesis, characterization of amide substituted dexibuprofen derivatives and their spectral, voltammetric and docking investigations for DNA binding interactions

- Synthesis of amide derivatives (Dex (2-4) of dexibuprofen (Dex-1) for anticancer potential.
- Kb and ∆ G values showed formation of more stable and spontaneous Dex-DNA adducts at pH 7.4 than at 4.7.
- Greater Dex-4 - DNA binding among all compounds at both blood and stomach pH.
- Binding site sizes (n) and docking revealed intercalation for Dex 2 & 4 and external binding for Dex 1 & 3.
- Spectroscopic, voltammetric and docking investigations showed consistency in the findings.

Three amide derivatives - methyl-2-[2-(4-isobutylphenyl)propanamido]propanoate (Dex-2), methyl 2-[2-(4-isobutylphenyl) propanamido]-3-phenylpropanoate (Dex-3) and methyl 2-[2-(4-isobutylphenyl)-propanamido]-4-methylpentanoate (Dex-4) of dexibuprofen (Dex-1) 2-(4-isobutylphenyl)propanoic acid were synthesized and conformed for structures by physical data and spectral analysis. Further, all the compounds were studied for their binding with ds.DNA through experimental (UV-visible/and fluorescence spectroscopy, cyclic voltammetry) and theoretical (molecular docking) techniques. Spectral and voltammetric responses as well as kinetic and thermodynamic data interpretations at stomach (4.7) and blood (7.4) pH and at human body temperature (37 °C) indicated spontaneous interaction of all the compounds with DNA via intercalation and external bindings. The binding constants (Kb) and Gibbs free energy changes (− ΔG) were evaluated greater at pH 7.4 attributing comparatively more significant binding of all the compounds with DNA at blood pH. Among all compounds, Dex-4 showed greater binding with DNA at both pH with greater Kb values i.e., {UV-visible: pH 4.7 (2.36 × 104 M− 1); pH 7.4 (2.42 × 104 M− 1), fluorescence: pH 4.7 (2.24 × 104 M− 1); pH 7.4 (2.56 × 104 M− 1) and CV: pH 4.7 (4.06 × 104 M− 1); pH 7.4 (4.89 × 104 M− 1)}. Binding site size (n) at both pH values was evaluated n ≥ 1 for Dex-2 and Dex-4 which assured intercalation as a major mode of interaction between compounds and DNA. For Dex-1 and Dex-3 (n) was evaluated n ≤ 1 at both pH values and the values n < 1 indicated the possibility of binding via groove or electrostatic interactions. Electrochemical processes were found diffusion controlled and diffusion coefficients (Do) for all the compounds - DNA adducts were evaluated lesser than unbound compounds. Docking studies further supported DNA binding evidences obtained from spectral and electrochemical investigations.

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