Some Novel Oxirane-Thiirane Derivatives: Synthesis, Molecular docking and Enzymatic Inhibition for Therapeutic Potential

In this study, a series of new oxirane and thiirane (2a–g), were assessed for their influence on various metabolic enzymes, including acetylcholinesterase (AChE) and human carbonic anhydrase isoenzymes (hCA I and hCA II). So, in the first stage, 1-chloro-3-phenothiazylpropanol-2 (2), methyl, methoxy-substituted oxirane, thiirane (2a and 2b), methyl, 1,2-aminopropanethiols (2c–2f), trifluorinated aminethiol derivative (2g), have been synthesized. The structures of synthesized compound were confirmed by IR, NMR analysis. Enzyme inhibition studies demonstrated that all these compounds exhibited potent inhibitory effects on all the target enzymes, surpassing the standard inhibitors, as evidenced by their IC50 and Ki values. The Ki values for the compounds concerning AChE, hCA I, and hCA II enzymes were in the ranges of 1.21 ± 0.072–12.64 ± 0.12, 5.93 ± 0.028- 81.87 ± 12.52 and 61.43 ± 10.01–344.22 ± 33.87 nM, respectively. Additionally, molecular docking studies were conducted to investigate further the binding interactions of the most potent inhibitors with enzyme active sites, revealing strong hydrogen bonding, π-stacking, and halogen interactions. These findings indicate that the synthesized compounds exhibit high affinity and specificity for the target enzymes, suggesting their potential for further development as therapeutic agents. Future studies will focus on optimizing the structural features of these compounds to enhance their selectivity and bioavailability, conducting in vivo evaluations to assess their pharmacokinetic and pharmacodynamic properties, and exploring their potential applications in the treatment of neurodegenerative and metabolic disorders.