Synthesis, characterization, crystal structure and bioactivities of novel enamine and pyrrole derivatives endowed with acetylcholinesterase, α-glycosidase and human carbonic anhydrase inhibition effects

Abstract

Presented research work is devoted to the synthesis of new heterocyclic compounds containing the ethyl ester fragment of acetate and glycine and the study of their crystal structure and biological activity. (Z)-Ethyl 2-(3-oxo-1,3-diphenylprop-1-enylamino)acetate (1) was first obtained on the base of the reaction of dibenzene methane with glycine ethyl ester hydrochloride in the presence of Y(OTF)3 catalyst in aqueous medium. At the same time, ethyl-3,5-diphenyl-1H-pyrrole-2-calboxylate (2) was synthesized from the interaction of enamine with tert-BuOK in the presence of tent-BuOH/DMFA solvent. The structure of new compounds has been studied by 1H, C-13 NMR. In addition, the crystal structure of ethyl-3,5-diphenyl-1H-pyrrole-2-carboxylate (2) is presented. The monoclinic, yellow crystals, with sizes 0.20 x 0.10 x 0.10 mm(3), one striped: a = 10.5340(6) E, b = 7.5101(5) E, c = 20.2352(15) angstrom, beta = 102.131(2)degrees, V = 1565.09(18) E-3, space group P2(1)/c, Z= 4, ds = 1.236 mg/m(3), mu = 0.080 mm(-1) were obtained. The crystalline compound keeps crystallographically independent molecules in the central bicyclic moiety. Compound 2 holds complex three-organic compound system consisting of pyrrole and benzol rings. In this study, the IC50 and K-i values of the compounds were calculated to compare their inhibition profiles on acetylcholinesterase (AChE), alpha-glycosidase and hCA I, and II isozymes. These compounds demonstrated Ki values in the low micromolar range for studied enzymes. The best inhibitor for hCA I and II isoenzymes and AChE was the (1) with Ki values of 47.21 +/- 5.06, 35.77 +/- 3.53 and 103.94 +/- 15.36 mu M, respectively. On the other hand, compound 2 showed the best inhibition profile against alpha-glycosidase with Ki of 63.76 +/- 7.12 mu M.