Molecular modeling of new thiazolyl-thiophene based compounds as antioxidant agents

The targeted N-(thiazol-2-yl)thiophene-2-carboxamide derivatives 4-9 were synthesized based on heterocyclization of the functionalized thiocarbamoyl precursors 1 and 2 with 2-chloroacetamido-thiazole (3). The synthesized compounds were studied using DFT/B3LYP level to explore their structural and electronic properties. The frontier molecular orbital, HOMO and LUMO, showed that HOMO was consisted mainly of heteroatoms non-bonding lone pairs of electrons and the pi-orbitals of the phenyl and thiophene rings with minor contribution from the thiazole nucleus of the non-bonding lone pairs. Furthermore, the investigated compounds had low energy gap (Delta EH-L), 1.64-2.62 eV, with the derivatives 7 and 4 having lowest and highest gap, respectively. The synthesized compounds exhibited good NLO properties due to their lower charge transfer resistance. The antioxidant activity for the synthesized thiazolyl-thiophene hybrids showed rational antioxidant effectiveness over DPPH technique. The results showed that hybrids 5, 7 and 9 exhibited respectable antioxidant with IC50 values (32.26 +/- 0.07, 27.31 +/- 0.23 and 23.17 +/- 0.36), respectively. However, thiazolyl-thiophene hybrids 4, 6 and 8 were shown tolerable IC50 values (43.28 +/- 0.14, 35.36 +/- 0.11 and 37.52 +/- 0.04), respectively against both of BHT (Butylated hydroxytoluene) and Ascorbic acid as references. The molecular docking estimation was also used on the generated thiazolyl-thiophene hybrids (PDB Code- 3OXI). The hybrids 4, 6 and 8 demonstrated a high binding affinity for the 3OXI amino acids. The docking results were satisfactory, and they mirrored the findings of the antioxidant study. (C) 2022 Elsevier B.V. All rights reserved.

Automated summary

The synthesized N-(thiazol-2-yl)thiophene-2-carboxamide derivatives showed good antioxidant activity, low energy gap, and strong nonlinear optical properties, making them promising candidates for various applications.