Design and synthesis of novel n-substituted pyrrole derivatives as potential antioxidant agents: In silico and DFT studies

In this work, various aryl-pyrroles 3a-d were synthesized by condensing different primary amines with 2,5-dimethoxytetrahydrofuran. Then, a Vilsmeier-Haack reaction was performed on the synthesized rings, affording the required formylated derivatives 4a-d with good yields up to 81%. These compounds were subsequently used to generate a series of new unsaturated α-β alkenes via condensation with two different activated methylenes. Beyond the standard spectroscopic characterization IR, ¹H and ¹³C-NMR spectra, X-ray diffraction analysis was also performed. Alternatively, molecular docking was used to predict and discuss possible interactions between these compounds and the active pockets of the crystal structure of water-forming NADPH Oxidase (PDB: 2CDU), revealing satisfying features regarding compounds 6a and 6b. Finally, additional computational investigations such as DFT computations and ADME profile screening were carried out on the top active compounds to gain some insight into their structure-activity correlations. A safe ADMET profile was predicted, and the relation between their electronic structures and their potential reactive sites was determined. KEY WORDS: Pyrrole derivatives, Antioxidant activity, Molecular docking, ADMET, DFT Bull. Chem. Soc. Ethiop. 2027, 41(1), 81-97. DOI: https://dx.doi.org/10.4314/bcse.v41i1.7