BHT-derived thiazolidin-4-ones: synthesis, radical scavenging activity, and in silico evaluation.

Abstract

Butylated hydroxytoluene (BHT) is a recognized antioxidant, while thiazolidin-4-ones are versatile scaffolds for bioactive molecule design. Here, BHT-functionalized thiazolidin-4-ones were synthesized with systematic variation at the N-3 position. Multicomponent synthetic strategies afforded thiazolidin-4-ones (4), a pyrazolo-thiazepinone derivative (5m), and a 1,2,3-triazole hybrid (7k). Antioxidant activity was evaluated using DPPH˙ and ABTS˙+ radical-scavenging assays and rat brain homogenates assessing ROS, nitrite, TBARS, and thiol levels. Compound 4d showed the strongest chemical radical-scavenging activity, while 4a and 4b were particularly active in the ABTS˙+ assay. Compound 4h showed intermediate chemical activity but also demonstrated biological effects. In conclusion, N-3 substitution modulated both chemical and biological antioxidant responses, and chemical radical-scavenging potency did not fully predict activity in the biological oxidative-stress model. Docking results showed no clear correlation with the experimental findings.