Design and synthesis of 2,4-dioxochroman-pyridinium-phenylacetamide derivatives as new anti-Alzheimer agents: in vitro and in silico studies |
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| Authors: | Marjan Mollazadeh Maryam Mohammadi-Khanaposhtani Homa Azizian Afsaneh Zonouzi Zahra Abdolahi Hamid Nadri Bagher Larijani Mahmood Biglar Mohammad Mahdavi |
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| Institution: | 1. School of Chemistry, College of Science, University of Tehran, Tehran, Iran;2. Cellular and Molecular Biology Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran;3. Department of Medicinal Chemistry, School of Pharmacy-International Campus, Iran University of Medical Sciences, Tehran, Iran;4. Department of Medicinal Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran;5. Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran |
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| Abstract: | 2,4-Dioxochroman-pyridinium-phenylacetamide derivatives 7a–n were synthesized and evaluated for their in vitro cholinesterase (ChE) inhibitory activities against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). Obtained results demonstrated that, among the synthesized compounds, two compounds, 7j and 7k , were more potent than the standard drug donepezil against BuChE and did not show cytotoxicity and carcinogenicity. Furthermore, through molecular modeling and molecular dynamic studies. we showed that these compounds can be located deep in the gorge cavity of BuChE and that they interacted with catalytic residues, acyl, and cholin-binding pockets of this enzyme. Support information |
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| Keywords: | 2 4-Dioxochroman Alzheimer agents: in vitro in silico phenylacetamide pyridinium |
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