5250-08-8

Upstream product

• 123-75-1 pyrrolidine 
• 50-00-0 formaldehyd 
• 100-06-1 1-(4-methoxyphenyl)ethanone 
• 25150-61-2 pyrrolidine hydrochloride 

Relevant academic research and scientific papers

Cytotoxicities of novel hydrazone compounds with pyrrolidine moiety: inhibition of mitochondrial respiration may be a possible mechanism of action for the cytotoxicity of new hydrazones

N,N’-Bis[1-aryl-3-pyrrolidine-1-yl)propylidene]hydrazine dihydrochlorides (R1–R7) were synthesized by the reaction of 2 mols of 1-aryl-3-(pyrrolidine-1-yl)-1-propanone hydrochlorides with 1 mol of hydrazine hydrate and reported for the first time with their detailed spectral analysis and cytotoxicities towards human hepatoma (Huh7) and breast cancer (T47D) cell lines. Compounds R2, R6, and R7 with the IC50 values of 5.16, 6.96, and 5.96 μM, respectively, showed higher cytotoxic potency than the reference compound 5-FU with 7.0 μM against Huh7 cell line. However, all compounds did not show better cytotoxic activities than 5-FU against T47D cell line at the conditions studied. The representative compound of series, R2, inhibited the mitochondrial respiration at 90, 165, and 265 μM concentrations in a dose dependent manner in liver homogenates, suggesting that mitochondrial respiration may be one of the contributing factor to the cytotoxicity of the compounds synthesized. The compounds R2, R6, and R7 can be chosen as the leader compounds of this study for further studies.

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 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.