Pharmacological assessment of disulfide–triazine hybrids: synthesis, enzyme inhibition, and molecular docking study

Abstract

Acetylcholinesterase (AChE) is indispensable for neurotransmission, while glutathione S-transferase (GST) plays a crucial role in cellular detoxification and protection. These enzymes are pivotal subjects in scientific investigations aimed at understanding neurological functions and maintaining cellular equilibrium. In pursuit of this objective, a set of disulfide–triazine hybrids (1, 2, and 3a–h) was effectively synthesized and methodically examined for their capacity to inhibit both AChE and GST (the Ki values for AChE range from 0.893 ± 0.117 μM to 7.961 ± 0.421 μM, while the IC₅₀ values fall within the range of 1.919–6.243 μM. For GST, the Ki values span from 2.093 ± 0.276 μM to 8.840 ± 1.934 μM, with IC₅₀ values ranging from 2.152 to 4.747 μM). After synthesizing the compounds and studying their biological effects, molecular docking analyses were conducted to understand how these compounds interact with target enzymes. This helped identify how the compounds bind and which amino acid residues are crucial for inhibition. The positive results highlight the potential of disulfide–triazine hybrids as strong inhibitors of AChE and GST, suggesting they could be further developed and optimized as therapeutic agents.