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, chloromethyl-2-(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 α-glycosidase 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±46.08µM. Against the physiologically dominant isoform hCA II, the novel compounds demonstrated Kis varying from 57.33±6.21 to 174.34±40.72µM. Also, these novel derivatives (M1-M4) effectively inhibited AChE, with Ki values in the range of 115.42±12.44 to 243.22±43.65µM. For BChE Ki values were found in the range of 94.33±9.14 to 189.45±35.88µM. For α-glycosidase the most effective Ki values of M4 and M3 were with Ki values of 32.86±7.88 and 37.63±4.08µM, respectively.