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

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 alpha-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 IC50 values. K-i values of novel group E1-E3 for hCA I, hCA II, AChE, and alpha-glycosidase enzymes were obtained in the ranges 4.08-15.04, 12.51-24.37, 52.07-81.21 and 1076.38-1287.55 mu M, 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, alpha-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.

Automated summary

This study focuses on the synthesis of thiocyanate-containing heterocyclic compounds and determines their inhibitory abilities against various enzymes. Theoretical calculations reveal the mechanism of substituting chloride with thiocyanate in aziridine derivatives. The synthesized compounds show potent inhibitory abilities and specifically inhibit hCA I and hCA II enzymes.