共查询到20条相似文献,搜索用时 15 毫秒
1.
Imen Boualia Chamseddine Derabli Raouf Boulcina Chawki Bensouici Muhammet Yildirim Arzu Birinci Yildirim El Hassen Mokrani Abdelmadjid Debache 《Archiv der Pharmazie》2019,352(11)
A series of bis(4‐amino‐5‐cyano‐pyrimidines) was synthesized and evaluated as dual inhibitors of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). To further explore the multifunctional properties of the new derivatives, their antioxidant and antibacterial activities were also tested. The results showed that most of these compounds could effectively inhibit AChE and BChE. Particularly, compound 7c exhibited the best AChE inhibitory activity (IC50 = 5.72 ± 1.53 μM), whereas compound 7h was identified as the most potent BChE inhibitor (IC50 = 12.19 ± 0.57 μM). Molecular modeling study revealed that compounds 7c, 7f , and 7b showed a higher inhibitory activity than that of galantamine against both AChE and BChE. Anticholinesterase activity of compounds 7h, 7b , and 7c was significant in vitro and in silico for both enzymes, since these compounds have hydrophobic rings (Br‐phenyl, dimethyl, and methoxyphenyl), which bind very well in both sites. In addition to cholinesterase inhibitory activities, these compounds showed different levels of antioxidant activities. Indeed, in the superoxide–dimethyl sulfoxide alkaline assay, compound 7j showed very high inhibition (IC50 = 0.37 ± 0.28 μM). Also, compound 7l exhibited strong and good antibacterial activity against Staphylococcus epidermidis and Staphylococcus aureus, respectively. Taking into account the results of biological evaluation, further modifications will be designed to increase potency on different targets. In this study, the obtained results can be a new starting point for further development of multifunctional agents for the treatment of Alzheimer's disease. 相似文献
2.
Synthesis and Anticholinergic Activity of 4‐hydroxycoumarin Derivatives Containing Substituted Benzyl‐1,2,3‐triazole Moiety 下载免费PDF全文
Sahar Mohammad Bagheri Mehdi Khoobi Hamid Nadri Alireza Moradi Saeed Emami Leili Jalili‐Baleh Farnaz Jafarpour Farshad Homayouni Moghadam Alireza Foroumadi Abbas Shafiee 《Chemical biology & drug design》2015,86(5):1215-1220
A series of 4‐hydroxycoumarin‐derived compounds 8a‐p containing N‐benzyl‐1,2,3‐triazole motif were designed as AChE inhibitors. The title compounds were obtained conveniently using multicomponent click reaction. The in vitro anticholinesterase evaluation of synthesized compounds against AChE and BuChE showed that some of them are potent and selective inhibitors of AChE. Among them, 2‐chlorobenzyl derivative 8k showed the most potent activity against AChE (IC50 = 0.18 μm ). Its activity was also superior to that of standard drug tacrine. The kinetic study and molecular docking simulation of the most potent compound 8k were also described. 相似文献
3.
Novel Potent and Selective Acetylcholinesterase Inhibitors as Potential Drugs for the Treatment of Alzheimer's Disease: Synthesis,Pharmacological Evaluation,and Molecular Modeling of Amino‐Alkyl‐Substituted Fluoro‐Chalcones Derivatives 下载免费PDF全文
Hao‐Ran Liu Chao Zhou Hao‐Qun Fan Jing‐Jing Tang Lin‐Bo Liu Xiao‐Hui Gao Qiu‐An Wang Wu‐Kun Liu 《Chemical biology & drug design》2015,86(4):517-522
A new series of‐fluoro chalcones‐substituted amino‐alkyl derivatives ( 3a?3l ) were designed, synthesized, characterized and evaluated for the inhibitory activity against acetylcholinesterase and butyrylcholinesterase. The results showed that the alteration of fluorine atom position and amino‐alkyl groups markedly influenced the activity and the selectivity of chalcone derivates in inhibiting acetylcholinesterase and butyrylcholinesterase. Among them, compound 3l possesses the most potent inhibitory against acetylcholinesterase (IC50 = 0.21 ± 0.03 μmol/L), and the highest selectivity for acetylcholinesterase over butyrylcholinesterase (IC50 (BuChE)/IC50 (AChE) = 65.0). Molecular modeling and enzyme kinetic study on compound 3l supported its dual acetylcholinesterase inhibitory profile, simultaneously binding at the catalytic active and peripheral anionic site of the enzyme. 相似文献
4.
Synthesis,Biological Evaluation,and Molecular Docking of 8‐imino‐2‐oxo‐2H,8H‐pyrano[2,3‐f]chromene Analogs: New Dual AChE Inhibitors as Potential Drugs for the Treatment of Alzheimer's Disease 下载免费PDF全文
Jeelan Basha Shaik Bhagath Kumar Palaka Mohan Penumala Siddhartha Eadlapalli Manidhar Darla Mark Dinakara Rao Ampasala Ramakrishna Vadde Damu Amooru Gangaiah 《Chemical biology & drug design》2016,88(1):43-53
Alzheimer's disease onset and progression are associated with the dysregulation of multiple and complex physiological processes, and a successful therapeutic approach should therefore address more than one target. In line with this modern paradigm, a series of 8‐imino‐2‐oxo‐2H,8H‐pyrano[2,3‐f]chromene analogs ( 4a – q ) were synthesized and evaluated for their multitarget‐directed activity on acetylcholinesterase, butyrylcholinesterase (BuChE), 2,2’‐azino‐bis(3‐ethylbenzthiazoline‐6‐sulfonic acid) (ABTS) radical, and amyloid‐β peptide (Aβ) specific targets for Alzheimer's disease therapy. Most of the synthesized compounds showed remarkable acetylcholinesterase inhibitory activities in low nm concentrations and good ABTS radical scavenging activity, however, no evidence of BuChE inhibitory activity. Among them, 3‐bromobenzylamide derivative 4m exhibited the best acetylcholinesterase inhibitory activity with IC50 value of 13 ± 1.4 nm which is 51‐fold superior to galantamine, a reference drug. Kinetic and molecular docking studies indicated 4m as mixed‐type inhibitor, binding simultaneously to catalytic active and peripheral anionic sites of acetylcholinesterase. Five compounds 4e , 4f , 4g , 4j , and 4k have shown 1.4‐ to 2.5‐fold of higher antioxidant activities than trolox. Interestingly, the most active compound 4m demonstrated dosage‐dependent acceleration of Aβ1?42 aggregation, which may reduce toxicity of oligomers. Overall, these results lead to discovery of fused tricyclic coumarins as promising dual binding site inhibitors of acetylcholinesterase and afford multifunctional compounds with potential impact for further pharmacological development in Alzheimer's therapy. 相似文献
5.
Design,synthesis, biological evaluation,and docking study of 4‐isochromanone hybrids bearing N‐benzyl pyridinium moiety as dual binding site acetylcholinesterase inhibitors (part II) 下载免费PDF全文
《Chemical biology & drug design》2018,91(3):756-762
A series of novel 4‐isochromanone compounds bearing N‐benzyl pyridinium moiety were designed and synthesized as acetylcholinesterase (AChE) inhibitors. The biological evaluation showed that most of the target compounds exhibited potent inhibitory activities against AChE. Among them, compound 1q possessed the strongest anti‐AChE activity with an IC50 value of 0.15 nm and high AChE/BuChE selectivity (SI > 5,000). Moreover, compound 1q had low toxicity in normal nerve cells and was relatively stable in rat plasma. Together, the current finding may provide a new approach for the discovery of novel anti‐Alzheimer's disease agents. 相似文献
6.
Novel pyridine‐2,4,6‐tricarbohydrazide thiourea compounds as small key organic molecules for the potential treatment of type‐2 diabetes mellitus: In vitro studies against yeast α‐ and β‐glucosidase and in silico molecular modeling 下载免费PDF全文
Tanzeel Ur. Rehman Sadaf Riaz Islam Ullah Khan Muhammad Ashraf Marek Bajda Alicja Gawalska Muhammad Yar 《Archiv der Pharmazie》2018,351(1)
A range of novel pyridine‐2,4,6‐tricarbohydrazide thiourea compounds ( 4a–i ) were synthesized in good to excellent yields (63–92%). The enzyme inhibitory potentials of these compounds were investigated against α‐ and β‐glucosidases because these enzymes play a crucial role in treating type‐2 diabetes mellitus (T2DM). As compared to the reference compound acarbose (IC50 38.22 ± 0.12 μM), compounds 4i (IC50 25.49 ± 0.67 μM), 4f (IC50 28.91 ± 0.43 μM), 4h (IC50 30.66 ± 0.52 μM), and 4e (IC50 35.01 ± 0.45 μM) delivered better inhibition against α‐glucosidase and were quite inactive/completely inactive against β‐glucosidase. The structure–activity relationship of these compounds was developed and elaborated with the help of molecular docking studies. 相似文献
7.
Reza Shamsimeymandi Yaghoub Pourshojaei Khalil Eskandari Maryam Mohammadi‐Khanaposhtani Ardavan Abiri Arash Khodadadi Amin Langarizadeh Fariba Sharififar Bagher Amirheidari Tahmineh Akbarzadeh Hania Lotfian Alireza Foroumadi Ali Asadipour 《Archiv der Pharmazie》2019,352(7)
A series of novel chroman‐4‐one derivatives were designed and synthesized successfully with good to excellent yield ( 3a–l ). In addition, the obtained products were evaluated for their cholinesterase (ChE) inhibitory activities. The results show that among the various synthesized compounds, analogs bearing the piperidinyl ethoxy side chain with 4‐hydroxybenzylidene on the 3‐positions of chroman‐4‐one ( 3l ) showed the most potent activity with respect to acetylcholinesterase (anti‐AChE activity; IC50 = 1.18 μM). In addition, the structure–activity relationship was studied and the results revealed that the electron‐donating groups on the aryl ring of the 3‐benzylidene fragment ( 3k , 3l ) resulted in the designed compounds to be more potent ChE inhibitors in comparison with those having electron‐withdrawing groups ( 3h ). In this category, the strongest ChE inhibition was found for the compound containing piperidine as cyclic amine, and a hydroxyl group (for AChE, compound 3l ) and fluoro group (for butyrylcholinesterase (BuChE, compound 3i ) on the para‐position of the aryl ring of the benzylidene group. The molecular docking and dynamics studies of the most potent compounds ( 3i and 3l against BuChE and AChE, respectively) demonstrated remarkable interactions with the binding pockets of the ChE enzymes and confirmed the results obtained through in vitro experiments. 相似文献
8.
Rabia Qamar Aamer Saeed Fayaz Ali Larik Qamar Abbas Mubashir Hassan Hussain Raza Sung‐Yum Seo 《Chemical biology & drug design》2019,93(2):123-131
A variety of 5‐(2H‐tetrazol‐5‐yl)‐4‐thioxo‐2‐(substituted phenyl)‐4,5‐dihydro‐1,3‐oxazin‐6‐ones ( 3a–k ) have been synthesized from 1,3‐oxazine‐5‐carbonitriles ( 2a–k ). The protocol represents an efficient, facile, and novel route from easily available precursors to unprecedented structures that share 1,3‐oxazine and tetrazole motifs of utmost value. All the synthesized compounds ( 3a–k ) were evaluated for their inhibitory potential against mushroom tyrosinase. Results revealed that all examined 1,3‐oxazine‐tetrazole hybrids exhibited significant tyrosinase inhibitory activity while compound 3d having 2‐bromophenyl moiety was the most potent among the series with IC50 value 0.0371 ± 0.0018 μM as compared to the reference kojic acid (IC50 = 16.832 ± 0.73 μM). Inhibitory kinetics showed that compound 3d behaves as a competitive inhibitor. The molecular docking analysis was performed against target protein to investigate the binding mode. Moreover, compounds 3j and 3k displayed superior DPPH radical scavenging activity than other analogues. 相似文献
9.
Harapriya Chakravarty Yaojun Ju Wen-Hua Chen Kin Y. Tam 《Drug development research》2020,81(2):242-255
With the surge in the cases of Alzheimer's disease (AD) over the years, several targets have been explored to curb the disease. Cholinesterases, namely acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE), remain to be the available targets that are amendable to currently approved treatments. In this study, a series of novel compounds based on tramiprosate, a highly specific amyloid beta (Aβ) inhibitor, was designed to inhibit AChE, BuChE, and Aβ aggregation. In particular, the addition of a pyridinium/isoquinolinium ring to the tramiprosate moiety (to give compounds 3a–j ) led to an increase in the binding affinity for the catalytic active site of cholinesterase, which was hampered by the presence of sulfonic acid. Exclusion of the sulfonic acid moiety led to a novel but effective class of cholinesterase inhibitors ( 9a–w ). in vitro Aβ aggregation inhibition assay indicated that compounds 3a–j , 9e – f , 9i–l , 9q , 9r , 9u–w , and 12 could inhibit over 10% Aβ aggregation at 1 mM concentration. Cholinesterase inhibition assay suggested that compounds 9g, 9h , 9o , and 9q–t exhibit over 70% inhibition on both AChE and BuChE at a concentration of 100 μM. Amongst the designed molecules, compound 9r (ca 18% at 1 mM) showed comparable inhibitory effect on the inhibition of Aβ aggregation with tramiprosate (ca 20% at 1 mM), along with impressive cholinesterase inhibitory potential (AChE IC50 = 13 μM and BuChE IC50 = 12 μM), acceptable toxicity and ability to pass through blood brain barrier, which could be used to ameliorate the phenotypes of AD in preclinical models. 相似文献
10.
Nakisa Ghamari Siavoush Dastmalchi Omid Zarei Jos‐Antonio Arias‐Montao David Reiner Fulya UstunAlkan Holger Stark Maryam Hamzeh‐Mivehroud 《Chemical biology & drug design》2020,95(2):279-290
Recently, multi‐target directed ligands have been of research interest for multifactorial disorders such as Alzheimer's disease (AD). Since H3 receptors (H3Rs) and cholinesterases are involved in pathophysiology of AD, identification of dual‐acting compounds capable of improving cholinergic neurotransmission is of importance in AD pharmacotherapy. In the present study, H3R antagonistic activity combined with anticholinesterase properties of two previously computationally identified lead compounds, that is, compound 3 (6‐chloro‐N‐methyl‐N‐[3‐(4‐methylpiperazin‐1‐yl)propyl]‐1H‐indole‐2‐carboxamide) and compound 4 (7‐chloro‐N‐[(1‐methylpiperidin‐3‐yl)methyl]‐1,2,3,4‐tetrahydroisoquinoline‐2‐carboxamide), was tested. Moreover, molecular docking and binding free energy calculations were conducted for binding mode and affinity prediction of studied ligands toward cholinesterases. Biological evaluations revealed inhibitory activity of ligands in nanomolar (compound 3 : H3R EC50 = 0.73 nM; compound 4 : H3R EC50 = 31 nM) and micromolar values (compound 3 : AChE IC50 = 9.09 µM, BuChE IC50 = 21.10 µM; compound 4 : AChE IC50 = 8.40 µM, BuChE IC50 = 4.93 µM) for H3R antagonism and cholinesterase inhibition, respectively. Binding free energies yielded good consistency with cholinesterase inhibitory profiles. The results of this study can be used for lead optimization where dual inhibitory activity on H3R and cholinesterases is needed. Such ligands can exert their biological activity in a synergistic manner resulting in higher potency and efficacy. 相似文献
11.
Biological evaluation of selected 3,4‐dihydro‐2(1H)‐quinoxalinones and 3,4‐dihydro‐1,4‐benzoxazin‐2‐ones: Molecular docking study 下载免费PDF全文
Jelena Petronijević Nenad Janković Tatjana P. Stanojković Nenad Joksimović Nađa Đ. Grozdanić Milan Vraneš Aleksandar Tot Zorica Bugarčić 《Archiv der Pharmazie》2018,351(5)
12.
Jian‐Jun Xi Ruo‐Yu He Jian‐Kang Zhang Zhao‐Bin Cai Rang‐Xiao Zhuang Yan‐Mei Zhao Yi‐Dan Shao Xu‐Wang Pan Ting‐Ting Shi Zuo‐Jun Dong Shou‐Rong Liu Li‐Min Kong 《Archiv der Pharmazie》2019,352(8)
A series of novel 3‐(thiophen‐2‐ylthio)pyridine derivatives as insulin‐like growth factor 1 receptor (IGF‐1R) inhibitors was designed and synthesized. IGF‐1R kinase inhibitory activities and cytotoxicities against HepG2 and WSU‐DLCL2 cell lines were tested. For all of these compounds, potent cancer cell proliferation inhibitory activities were observed, but not through the inhibition of IGR‐1R. Selected compounds were further screened against various kinases. Typical compound 22 (50% inhibitory concentration [IC50] values, HepG2: 2.98 ± 1.11 μM and WSU‐DLCL2: 4.34 ± 0.84 μM) exhibited good inhibitory activities against fibroblast growth factor receptor‐2 (FGFR2), FGFR3, epidermal growth factor receptor, Janus kinase, and RON (receptor originated from Nantes), with IC50 values ranging from 2.14 to 12.20 μM. Additionally, the cell‐cycle analysis showed that compound 22 could arrest HepG2 cells in the G1/G0 phase. Taken together, all the experiments confirmed that the compounds in this series were multitarget anticancer agents worth further optimizing. 相似文献
13.
Synthesis,p38α MAP kinase inhibition,anti‐inflammatory activity,and molecular docking studies of 1,2,4‐triazole‐based benzothiazole‐2‐amines 下载免费PDF全文
14.
Structure–activity relationship studies of benzyl‐, phenethyl‐, and pyridyl‐substituted tetrahydroacridin‐9‐amines as multitargeting agents to treat Alzheimer's disease 下载免费PDF全文
Wesseem Osman Tarek Mohamed Victor Munsing Sit Maryam S. Vasefi Michael A. Beazely Praveen P. N. Rao 《Chemical biology & drug design》2016,88(5):710-723
A library of substituted tetrahydroacridin‐9‐amine derivatives were designed, synthesized, and evaluated as dual cholinesterase and amyloid aggregation inhibitors. Compound 8e (N‐(3,4‐dimethoxybenzyl)‐1,2,3,4‐tetrahydroacridin‐9‐amine) was identified as a potent inhibitor of butyrylcholinesterase (BuChE IC50 = 20 nm ; AChE IC50 = 2.2 μm ) and was able to inhibit amyloid aggregation (40% inhibition at 25 μm ). Compounds 9e (6‐chloro‐N‐(3,4‐dimethoxybenzyl)‐1,2,3,4‐tetrahydroacridin‐9‐amine, AChE IC50 = 0.8 μm ; BuChE IC50 = 1.4 μm ; Aβ‐aggregation inhibition = 75.7% inhibition at 25 μm ) and 11b (6‐chloro‐N‐(3,4‐dimethoxyphenethyl)‐1,2,3,4‐tetrahydroacridin‐9‐amine, AChE IC50 = 0.6 μm ; BuChE IC50 = 1.9 μm ; Aβ‐aggregation inhibition = 85.9% inhibition at 25 μm ) were identified as the best compounds with dual cholinesterase and amyloid aggregation inhibition. The picolylamine‐substituted compound 12c (6‐chloro‐N‐(pyridin‐2‐ylmethyl)‐1,2,3,4‐tetrahydroacridin‐9‐amine) was the most potent AChE inhibitor (IC50 = 90 nm ). These investigations demonstrate the utility of 3,4‐dimethoxyphenyl substituent as a novel pharmacophore possessing dual cholinesterase inhibition and anti‐Aβ‐aggregation properties that can be used in the design and development of small molecules with multitargeting ability to treat Alzheimer's disease. 相似文献
15.
Design,synthesis, and biological evaluation of novel 1,2‐diaryl‐4‐substituted‐benzylidene‐5(4H)‐imidazolone derivatives as cytotoxic agents and COX‐2/LOX inhibitors 下载免费PDF全文
16.
Syntheses,Cholinesterases Inhibition,and Molecular Docking Studies of Pyrido[2,3‐b]pyrazine Derivatives 下载免费PDF全文
Abdul Hameed Syeda T. Zehra Syed J. A. Shah Khalid M. Khan Rima D. Alharthy Norbert Furtmann Jürgen Bajorath Muhammad N. Tahir Jamshed Iqbal 《Chemical biology & drug design》2015,86(5):1115-1120
Cholinesterases, acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), have a role in cholinergic deficit which evidently leads to Alzheimer's disease (AD). Inhibition of cholinesterases with small molecules is an attractive strategy in AD therapy. This study demonstrates synthesis of pyrido[2,3‐b]pyrazines ( 6a ‐ 6q ) series, their inhibitory activities against both cholinesterases, AChE and BChE, and molecular docking studies. The bioactivities data of pyrido[2,3‐b]pyrazines showed 3‐(3′‐nitrophenyl)pyrido[2,3‐b]pyrazine 6n a potent dual inhibitor among the series against both AChE and BChE with IC50 values of 0.466 ± 0.121 and 1.89 ± 0.05 μm , respectively. The analogues 3‐(3′‐methylphenyl)pyrido[2,3‐b]pyrazine 6c and 3‐(3′‐fluorophenyl)pyrido[2,3‐b]pyrazine 6f were found to be selective inhibition for BChE with IC50 values of 0.583 ± 0.052 μm and AChE with IC50 value of 0.899 ± 0.10 μm , respectively. Molecular docking studies of the active compounds suggested the putative binding modes with cholinesterases. The potent compounds among the series could potentially serves as good leads for the development of new cholinesterase inhibitors. 相似文献
17.
A novel series of N′‐(2‐(3,5‐disubstituted‐4H‐1,2,4‐triazol‐4‐yl)acetyl)‐6/7/8‐substituted‐2‐oxo‐2H‐chromen‐3‐carbohydrazides were synthesized and studied for their α‐glucosidase inhibition activity. Most of the synthesized compounds exhibited potential α‐glucosidase inhibition activity with IC50 values ranging from 0.96 ± 0.02 to 32.86 ± 0.73 µg/ml. Among them, compounds 3e and 4e , having a methoxy group on the coumarin ring, proved to be the most potent ones, showing an enzyme inhibition activity with IC50 = 0.96 ± 0.02 and 1.44 ± 0.06 µg/ml, respectively. The kinetic study through Lineweaver–Burk plots revealed that the inhibition mechanism of the most active compounds 3d, 3e, 4d , and 4e , on the α‐glucosidase activity, was found to be in the competitive mode. 相似文献
18.
Wei Jia Yanfang Zhao Rongdong Li Yanjiao Wu Zebiao Li Ping Gong 《Archiv der Pharmazie》2009,342(9):507-512
A series of 9‐methoxy‐6H‐[1]benzothiopyrano[4,3‐b]quinolin‐10‐ols with a Mannich side chain were synthesized and evaluated for their anti‐Hepatitis B virus (HBV) activity in HepG2.2.15 cells. Some compounds showed significant anti‐HBV activity with IC50 values less than 41 μM. Among them, compound 9b was the most effective anti‐HBV agent (IC50 = 1.7 μM, SI = 60.3). 相似文献
19.
Synthesis,enzyme inhibitory kinetics,and computational studies of novel 1‐(2‐(4‐isobutylphenyl) propanoyl)‐3‐arylthioureas as Jack bean urease inhibitors 下载免费PDF全文
《Chemical biology & drug design》2018,91(2):434-447
In this article, synthesis of a novel 1‐(2‐(4‐isobutylphenyl)propanoyl)‐3‐arylthioureas ( 4a–j) as jack bean urease inhibitors has been described. Freshly prepared 2‐(4‐isobutylphenyl) propanoyl isothiocyanate was treated with substituted aromatic anilines in one pot using anhydrous acetone. The compounds 4e, 4h, and 4j showed IC50 values 0.0086 nm , 0.0081 nm , and 0.0094 nm , respectively. The enzyme inhibitory kinetics results showed that compound 4h inhibit the enzyme competitively while derivatives 4e and 4j are the mixed type inhibitors. The compound 4h reversibly binds the urease enzyme showing Ki value 0.0012 nm . The Ki values for 4e and 4j are 0.0025 nm and 0.003 nm , respectively. The antioxidant activity results reflected that compounds 4b, 4i, and 4j showed excellent radical scavenging activity. Moreover, the cytotoxic activity of the target compounds was evaluated using brine shrimp assay and it was found that all of the synthesized compounds exhibited no cytotoxic effects to brine shrimps. The computational molecular docking and molecular dynamic simulation of title compounds were also performed, and results showed that the wet laboratory findings are in good agreement to the dry laboratory results. Based upon our results, it is proposed that compound 4h may act as a lead candidate to design the clinically useful urease inhibitors. 相似文献
20.
Bajda M Kuder KJ Lażewska D Kieć-Kononowicz K Więckowska A Ignasik M Guzior N Jończyk J Malawska B 《Archiv der Pharmazie》2012,345(8):591-597
The study presents novel biological properties of diether derivatives of homo‐ or substituted piperidine ligands of the histamine H3 receptor. The compounds were evaluated for their inhibitory potency against acetylcholinesterase (AChE) from the electric eel and butyrylcholinesterase (BuChE) from horse serum. The most interesting multifunctional compound 13 displayed high affinity for the cloned hH3R (Ki = 3.48 nM) and moderate inhibitory potency against both enzymes (IC50 AChE = 7.91 µM and BuChE = 4.97 µM). Molecular modeling studies revealed interactions with key amino acid residues in the homology model of histamine H3 receptor ligands, as well as the binding model for AChE and BuChE in the catalytic and peripheral active sites. 相似文献