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

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 K-i 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) pro-pylidene] hydrazine dihydrochlorides, P4, in P-series, and N, N'-bis[1-(4-chlorophenyl)-3-(pyrrolidine-1-yl) pro-pylidene] hydrazine dihydrochlorides, R5, in R-series were the most powerful compounds against hCA I with the K-i 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 K-i 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 K-i 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 K-i 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 K-i values of 119 +/- 20 nM, 88 +/- 14 nM, respectively.