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Shahrzad Ghafary Roshanak Ghobadian Mohammad Mahdavi Hamid Nadri Alireza Moradi Tahmineh Akbarzadeh Zahra Najafi Mohammad Sharifzadeh Najmeh Edraki Farshad Homayouni Moghadam Mohsen Amini 《Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences》2020,28(2):463
BackgroundAcetylcholine deficiencies in hippocampus and cortex, aggregation of β-amyloid, and β-secretase over activity have been introduced as main reasons in pathogenesis of Alzheimer’s disease.MethodsColorimetric Ellman’s method was used for determination of IC50 value in AChE and BChE inhibitory activity. The kinetic studies, neuroprotective and β-secretase inhibitory activities, evaluation of inhibitory potency on β-amyloid (Aβ) aggregations induced by AChE, and docking study were performed for prediction of the mechanism of action.Result and discussionA new series of cinnamic acids-tryptamine hybrid was designed, synthesized, and evaluated as dual cholinesterase inhibitors. These compounds demonstrated in-vitro inhibitory activities against acetyl cholinesterase (AChE) and butyryl cholinesterase (BChE). Among of these synthesized compounds, (E)-N-(2-(1H-indol-3-yl)ethyl)-3-(3,4-dimethoxyphenyl)acrylamide (5q) demonstrated the most potent AChE inhibitory activity (IC50 = 11.51 μM) and (E)-N-(2-(1H-indol-3-yl)ethyl)-3-(2-chlorophenyl)acrylamide (5b) were the best anti-BChE (IC50 = 1.95 μM) compounds. In addition, the molecular modeling and kinetic studies depicted 5q and 5b were mixed type inhibitor and bound with both the peripheral anionic site (PAS) and catalytic sites (CAS) of AChE and BChE. Moreover, compound 5q showed mild neuroprotective in PC12 cell line and weak β-secretase inhibitory activities. This compound also inhibited aggregation of β-amyloid (Aβ) in self-induced peptide aggregation test at concentration of 10 μM.ConclusionIt is worth noting that both the kinetic study and the molecular modeling of 5q and 5b depicted that these compounds simultaneously interacted with both the catalytic active site and the peripheral anionic site of AChE and BChE. These findings match with those resulted data from the enzyme inhibition assay. Graphical abstractOpen in a separate windowA new series of cinnamic-derived acids-tryptamine hybrid derivatives were designed, synthesized and evaluated as butyrylcholinesterase (BChE) and acetylcholinesterase (AChE) inhibitors and neuroprotective agents. Compound 5b and 5q, as the more potent compounds, interacted with both the peripheral site and the choline binding site having mixed type inhibition. Results suggested that derivatives have a therapeutic potential for the treatment of AD.Electronic supplementary materialThe online version of this article (10.1007/s40199-020-00346-9) contains supplementary material, which is available to authorized users. 相似文献
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Psychometric evaluation of the Persian version of the Type 2 Diabetes and Health Promotion Scale (T2DHPS): a diabetes‐specific measure of lifestyle 下载免费PDF全文
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Rezayat Arash Akhavan Sahebdel Saeed Jafari Sina Kabirian Ali Rahnejat Amir Mohsen Farahani Ramin Hamidi Mosaed Reza Nour Mohammad Ghasemi 《The Psychiatric quarterly》2020,91(4):1265-1290
Psychiatric Quarterly - Our study systematically reviews articles about the prevalence of Post-traumatic Stress Disorder (PTSD) among children and adolescents, aiming to evaluate its prevalence... 相似文献
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Shirazi Mohsen Ahmad Akhoundi Mohammad Sadegh Javadi Ehsan Kamali Abbas Motahhari Pouria Rashidpour Mahsa Chiniforush Nasim 《Lasers in medical science》2015,30(2):713-718
Lasers in Medical Science - Low-level laser has been indicated to have the capability to facilitate the differentiation of the osteoclastic and osteoblastic cells which are responsible for the bone... 相似文献