Synthesis, docking study and neuroprotective effects of some novel pyrano[3,2-c]chromene derivatives bearing morpholine/phenylpiperazine moiety

Publication date: Available online 19 May 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Bilqees Sameem, Mina Saeedi, Mohammad Mahdavi, Hamid Nadri, Farshad Homayouni Moghadam, Najmeh Edraki, Muhammad Imran Khan, Mohsen Amini
Novel pyrano[3,2-c]chromene derivatives bearing morpholine/phenylpiperazine moiety were synthesized and evaluated against acetylcholinestrase (AChE) and butylcholinestrase (BuChE). Among the synthesized compounds, N-(3-cyano-4-(4-methoxyphenyl)-5-oxo-4,5-dihydropyrano[3,2-c]chromen-2-yl)-2-(4-phenylpiperazin-1-yl)acetamide (6c) exhibited the highest acetylcholinestrase inhibitory (AChEI) activity (IC50 = 1.12 µM) and most of them showed moderate butylcholinestrase inhibitory activity (BChEI). Kinetic study of compound 6c confirmed mixed type of inhibition towards AChE which was in covenant with the results obtained from docking study. Also, it was evaluated against β-secretase which demonstrated low activity (inhibition percentage: 18%). It should be noted that compounds 6c, 7b, 6g, and 7d showed significant neuroprotective effects against H2O2-induced PC12 oxidative stress.

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