Here we report the two-step synthesis of 8 new cyclopentaquinoline derivatives as modifications of the tetrahydroacridine structure. Next, the biological assessment of each of them was performed. Based on the obtained results we identified 6-chloro--[2-(2,3-dihydro--cyclopenta[b]quinolin-9-ylamino)-hexyl]]-nicotinamide hydrochloride () as the most promising compound with inhibitory potencies against EeAChE and EqBuChE in the low nanomolar level 67 and 153 nM, respectively. Moreover, compound is non-hepatotoxic, able to inhibit amyloid beta aggregation, and shows a mix-type of cholinesterase's inhibition. The mixed type of inhibition of the compound was confirmed by molecular modeling. Then, yeast three-hybrid (Y3H) technology was used to confirm the known ligand-receptor interactions. New derivatives do not show antioxidant activity (confirmed by the use of two different tests). A pKa assay method was developed to identify the basic physicochemical properties of compound. A LogP assay confirmed that compound fulfills Lipinsky's rule of five.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6386991 | PMC |
| http://dx.doi.org/10.3390/ijms20030498 | DOI Listing |
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