Novel Sulphadoxine-Triazole Hybrids: Synthesis, Antioxidant Activity and Molecular Docking toward Biological Targets

Abstract

Click chemistry was used in this study as an effective and selective synthetic method to successfully create a number of novel heterocyclic triazole derivatives based on the medication sulphadoxine.  Sulphadoxine was first modified by a diazotization process with sodium nitrite and hydrochloric acid, and then the azide derivative (S) was obtained by substitution with sodium azide.  The second stage was reacting p-hydroxybenzaldehyde with 3-bromo-1-propyne to produce the alkyne derivative (A).  A number of novel chalcone derivatives (A1–A3) were created by Claisen–Schmidt condensation of this molecule with different aromatic ketones. The target triazole derivatives (E1–E3) were obtained in good yields by reacting the azide-functionalized sulphadoxine derivative (S) with the synthesized chalcones (A1–A3) via copper-catalyzed azide–alkyne cycloaddition (CuAAC) click chemistry.  Fourier-transform infrared (FT-IR) spectroscopy and thin-layer chromatography (TLC) were used to verify the chemical structures of all produced substances. Additionally, the antioxidant activity of a few chosen derivatives was assessed; the findings showed that several molecules had encouraging antioxidant potential.  In order to support the synthesized derivatives' possible biological activity, molecular docking experiments were also carried out to examine the binding interactions and affinity of the derivatives toward certain biological targets.  Overall, the results indicate that the recently produced triazole compounds based on sulphadoxine are interesting scaffolds for additional biological testing and potential therapeutic development.