Investigation of inhibitory properties of some hydrazone compounds on hCA I, hCA II and AChE enzymes

Abstract

Recently, inhibition of carbonic anhydrase (hCA) and acetylcholinesterase (AChE) have appeared as a promising approach for pharmacological intervention in a variety of disorders such as glaucoma, epilepsy, obesity, cancer, and Alzheimer’s disease. Keeping this in mind, N,N?-bis[(1-aryl-3-heteroaryl)propylidene]hydrazine dihydrochlorides, N1-N11, P1, P4-P8, and R1-R6, were synthesized to investigate their inhibitory activity against hCA I, hCA II, and AChE enzymes. All compounds in N, P, and R-series inhibited hCAs (I and II) and AChE more efficiently than the reference compounds acetazolamide (AZA), and tacrine. According to the activity results, the most effective inhibitory compounds were in R-series with the Ki values of 203?±?55–473?±?67?nM and 200?±?34–419?±?94?nM on hCA I, and hCA II, respectively. N,N?-Bis[1-(4-fluorophenyl)-3-(morpholine-4-yl)propylidene]hydrazine dihydrochlorides, N8, in N-series, N,N?-Bis[1-(4-hydroxyphenyl)-3-(piperidine-1-yl)propylidene]hydrazine dihydrochlorides, P4, in P-series, and N,N?-bis[1-(4-chlorophenyl)-3-(pyrrolidine-1-yl)propylidene]hydrazine dihydrochlorides, R5, in R-series were the most powerful compounds against hCA I with the Ki values of 438?±?65?nM, 344?±?64?nM, and 203?±?55?nM, respectively. Similarly, N8, P4, and R5 efficiently inhibited hCA II isoenzyme with the Ki values of 405?±?60?nM, 327?±?80?nM, and 200?±?34?nM, respectively. On the other hand, P-series compounds had notable inhibitory effect against AChE than the reference compound tacrine and the Ki values were between 66?±?20?nM and 128?±?36?nM. N,N?-Bis[1-(4-fluorophenyl)-3-(piperidine-1-yl)propylidene]hydrazine dihydrochlorides, P7, was the most potent compound on AChE with the Ki value of 66?±?20?nM. The other most promising compounds, N,N?-bis[1-(4-hydroxyphenyl)-3-(morpholine-4-yl)propylidene]hydrazine dihydrochlorides, N4 in N-series and N,N?-bis[1-(4-hydroxyphenyl)-3-(pyrrolidine-1-yl)propylidene]hydrazine dihydrochlorides, R4 in R-series were againts AChE with the Ki values of 119?±?20?nM, 88?±?14?nM, respectively.