Synthesis and examination of 1,2,4‐triazine‐sulfonamide hybrids as potential inhibitory drugs: Inhibition effects on AChE and GST enzymes in silico and in vitro conditions

Abstract The crucial functions of acetylcholinesterase (AChE) in neurotransmission and glutathione S ‐transferase (GST) in detoxification and cellular protection underscore their pivotal roles as key enzymes, essential for maintaining the integrity of neurological and cellular homeostasis. For this purpose, a series of 1,2,4‐triazine‐sulfonamide hybrids ( 3a – r ) was successfully synthesized, and subsequently evaluated for their inhibitory effects on AChE and GST. The investigation was complemented by molecular docking studies and ADMET (Absorption, Distribution, Metabolism, Excretion, and Toxicity) predictions. The synthesized hybrids demonstrated significant promise in inhibiting both AChE and GST activities. Molecular docking analyses provided insights into the interactions between the compounds and the target enzymes, shedding light on potential binding modes and key amino acid residues involved. Furthermore, the study benefited from ADMET predictions, offering valuable information on the compounds' pharmacokinetic properties and potential toxicity. The promising results obtained from this comprehensive approach highlight the potential of these 1,2,4‐triazine‐sulfonamide hybrids as effective inhibitors of AChE and GST, paving the way for further development and optimization in the pursuit of novel therapeutic agents.