Some Thiocyanate Containing Heterocyclic Compounds: Synthesis, Bioactivity and Molecular Docking Study

Abstract

This study focuses on the synthesis of some thiocyanate containing heterocyclic compounds. Theoretical calculations are conducted to genergate a mechanism for substituting chloride with thiocyanate in 2‐(chloromethyl)aziridine derivatives, which result in formation of thiocyanate‐based aziridine derivatives. Computations reveal that the two similar reactions have a different reaction profile, namely E1 formation is endergonic (+32.8 kcal/mol) while the E2 formation is exergonic (−62.8 kcal/mol). All heterocyclic molecules were determined for human carbonic anhydrase I, II (hCAs I and II), acetylcholinesterase (AChE), and α‐glycosidase inhibitory abilities. Results indicated that all the synthetic compounds exhibited potent inhibitory abilities against all targets as compared to the standard inhibitors, revealed by IC ₅₀ values. K _i values of novel group E1–E3 for hCA I, hCA II, AChE, and α‐glycosidase enzymes were obtained in the ranges 4.08‐15.04, 12.51–24.37, 52.07–81.21 and 1076.38–1287.55 μM, respectively. Molecular modeling results have shown that the most active molecules have binding affinity with −6.204, −4.423, −6.298, and −6.623 kcal/mol against hCA II, hCA I, α‐glycosidase, and AChE enzymes, respectively. Thiocyanate moiety specifically inhibited hCA I and hCA II enzymes. CA inhibitors have the ability to dilate retinal capillaries and suppress capillary blockage.