研究某些腙类化合物对 hCA I、hCA II 和 AChE 酶的抑制特性。
Investigation of inhibitory properties of some hydrazone compounds on hCA I, hCA II and AChE enzymes.
机构信息
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Selcuk University, Konya, Turkey.
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Atatürk University, Erzurum, Turkey.
出版信息
Bioorg Chem. 2019 May;86:316-321. doi: 10.1016/j.bioorg.2019.02.008. Epub 2019 Feb 4.
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 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 K 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 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 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 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 values of 119 ± 20 nM, 88 ± 14 nM, respectively.
最近，抑制碳酸酐酶（hCA）和乙酰胆碱酯酶（AChE）已成为治疗多种疾病（如青光眼、癫痫、肥胖症、癌症和阿尔茨海默病）的一种有前途的药物干预方法。考虑到这一点，我们合成了 N,N'-双[(1-芳基-3-杂芳基)丙二烯基]肼二盐酸盐（N1-N11、P1、P4-P8 和 R1-R6），以研究它们对 hCA I、hCA II 和 AChE 酶的抑制活性。所有 N、P 和 R 系列化合物对 hCAs（I 和 II）和 AChE 的抑制活性均优于参考化合物乙酰唑胺（AZA）和他克林。根据活性结果，最有效的抑制化合物是 R 系列，其对 hCA I 和 hCA II 的 K 值分别为 203±55-473±67 nM 和 200±34-419±94 nM。在 N 系列中，N,N'-双[1-(4-氟苯基)-3-(吗啉-4-基)丙二烯基]肼二盐酸盐（N8），在 P 系列中，N,N'-双[1-(4-羟基苯基)-3-(哌啶-1-基)丙二烯基]肼二盐酸盐（P4），在 R 系列中，N,N'-双[1-(4-氯苯基)-3-(吡咯烷-1-基)丙二烯基]肼二盐酸盐（R5）是对 hCA I 抑制作用最强的化合物，其 K 值分别为 438±65 nM、344±64 nM 和 203±55 nM。同样，N8、P4 和 R5 对 hCA II 同工酶也具有很强的抑制作用，其 K 值分别为 405±60 nM、327±80 nM 和 200±34 nM。另一方面，与参考化合物他克林相比，P 系列化合物对 AChE 具有显著的抑制作用，K 值在 66±20 nM 和 128±36 nM 之间。N,N'-双[1-(4-氟苯基)-3-(哌啶-1-基)丙二烯基]肼二盐酸盐（P7）是对 AChE 抑制作用最强的化合物，K 值为 66±20 nM。其他最有前途的化合物是 N,N'-双[1-(4-羟基苯基)-3-(吗啉-4-基)丙二烯基]肼二盐酸盐（N4）和 N,N'-双[1-(4-羟基苯基)-3-(吡咯烷-1-基)丙二烯基]肼二盐酸盐（R4），它们对 AChE 的 K 值分别为 119±20 nM 和 88±14 nM。
Zotero 插件