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Synthesis and anticholinesterase activity of novel non-hepatotoxic naphthyridine-11-amine derivatives

  • Belma Zengin Kurt
Original Article

Abstract

In the present study, 14 novel naphthyridine-11-amine derivatives were synthesized and their inhibitory effects on acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) were evaluated. 12-(4-Fluorophenyl)-1,2,3,4,7,8,9,10-octahydrodibenzo[b,g][1, 8]naphthyridin-11-amine (4a) was found to be the most potent AChE inhibitor with IC50 value of 0.091 µM, and 12-(2,3-dimethoxyphenyl)-1,2,3,4,7,8,9,10-octahydrodibenzo[b,g][1,8]naphthyridin-11-amine (4h) exhibited the strongest inhibition against BuChE with IC50 value of 0.182 µM. Additionally, hepatocellular carcinoma (HepG2) cell cytotoxicity assay for the synthesized compounds was investigated and the results showed negligible cell death. Log P values of the synthesized compounds were also calculated using ChemSketch program. Moreover, the blood–brain barrier (BBB) permeability of the potent AChE inhibitor (4a) was assessed by the widely used parallel artificial membrane permeability assay (PAMPA-BBB). The results showed that 4a is capable of crossing the BBB.

Graphical abstract

Keywords

Naphthyridine Anticholinesterase activity Cell cytotoxicity Blood–brain barrier permeability 

Notes

Acknowledgements

This work was supported by the Bezmialem Research Fund of the Bezmialem Vakif University. Project Number: 3.2018/5.

Supplementary material

11030_2018_9897_MOESM1_ESM.doc (1.3 mb)
Supplementary material 1 (DOC 1363 kb)

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Copyright information

© Springer Nature Switzerland AG 2018

Authors and Affiliations

  1. 1.Department of Pharmaceutical Chemistry, Faculty of PharmacyBezmialem Vakif UniversityIstanbulTurkey

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