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 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.