Molecular modeling and antioxidant evaluation of new di-2-thienyl ketones festooned with thiazole or pyridine moiety.

• Synthesis of new functionalized dithienyl ketones linked thiazole and/or pyridine. • The DFT study was conducted to determine the HOMO-LUMO energies and Fukui's indices. • The local relative electrophilicity and nucleophilicity descriptors were calculated. • Antioxidant activity of the synthesized dithienyl ketone derivatives was explored. • The computational docking processes were examined toward (PDB Code: 2AS1). Different novel derivatives of 5-(5-bromothiophen-2-oyl)-2-(phenylamino)thiophen-3-yl) ethylidene-hydrazinylthiazole and 2-(5-bromothiophen-2-oyl)thieno[2,3-b]pyridine were prepared by utilizing the synthesized (5-bromothien-2-yl) (4-acetyl-3-methyl-5-phenylaminothien-2-yl) ketone (3) as a precursor. The electronic and chemical reactivity of the derivatives toward nucleophilic, electrophilic, and radical attacks were evaluated based on quantum chemical calculations; the highest occupied molecular orbital (HOMO)-lowest occupied molecular orbital (LUMO) energies and Fukui indices were determined using the density functional theory (DFT) at Becke, 3-parameter, Lee–Yang–Parr (B3LYP) level. Compound 6 possessed the lowest HOMO energy value (E H), LUMO energy value (E L), and energy gap (ΔE H-L). Significant inhibition percentage was observed while evaluating the antioxidant activities of the synthesized di-2-thienyl ketones 3–8 using vitamin C as a reference drug. The highest antioxidant activity with an IC 50 value of 39.85 and 34.37 µM was observed for the di-2-thienyl ketones 5 and 6 incorporating thiazole ring. Meanwhile, the rest of the di-2-thienyl ketone derivatives displayed reasonable IC 50 values from 51.60 to 68.88 µM. This experimental data was supported by molecular docking analysis of the interactions between di-2-thienyl ketone compounds and cytochrome c peroxidase (PDB Code: 2AS1) applied through Molecular Operating Environment (MOE) v10.2015.10. [Display omitted] [ABSTRACT FROM AUTHOR]