Novel functionally substituted esters based on sodium diethyldithiocarbamate derivatives: Synthesis, characterization, biological activity and molecular docking studies

Abstract

Alkylation of sodium diethyldithiocarbamate with allyl-2-chloroacetate, allyl-3-chloropropionate, chloromethyl2-(tetrahydrofuran-2-yl)acetate, and 4-(chloromethyl)-1,3-dioxolane in the aqueous medium synthesized functionally substituted esters of N, N-dietyleditiocarbamic acid (M1-M4). Most active compounds were docked into the catalytic active site of the enzyme. We identified that acetate moiety for inhibition of hCA I, hCA II, and aglycosidase and dioxolane and thiocarbamic acid moieties for inhibition of AChE and BChE enzymes are very important. The hCA I isoform was inhibited by these novel functionally substituted esters based on sodium diethyldithiocarbamate derivatives (M1-M4) in low micromolar levels, the Ki of which differed between 48.03 +/- 9.77 and 188.42 +/- 46.08 mu M. Against the physiologically dominant isoform hCA II, the novel compounds demonstrated Kis varying from 57.33 +/- 6.21 to 174.34 +/- 40.72 mu M. Also, these novel derivatives (M1-M4) effectively inhibited AChE, with Ki values in the range of 115.42 +/- 12.44 to 243.22 +/- 43.65 mu M. For BChE Ki values were found in the range of 94.33 +/- 9.14 to 189.45 +/- 35.88 mu M. For alpha-glycosidase the most effective Ki values of M4 and M3 were with Ki values of 32.86 +/- 7.88 and 37.63 +/- 4.08 mu M, respectively.