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Int. J. Mol. Sci. 2012, 13(8), 10067-10090; doi:10.3390/ijms130810067
Article

2,3-Dihydro-1H-cyclopenta[b]quinoline Derivatives as Acetylcholinesterase Inhibitors—Synthesis, Radiolabeling and Biodistribution

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Received: 14 June 2012; in revised form: 7 July 2012 / Accepted: 6 August 2012 / Published: 13 August 2012
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
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Abstract: In the present study we describe the synthesis and biological assessment of new tacrine analogs in the course of inhibition of acetylcholinesterase. The obtained molecules were synthesized in a condensation reaction between activated 6-BOC-hydrazinopyridine-3-carboxylic acid and 8-aminoalkyl derivatives of 2,3-dihydro-1H-cyclopenta[b]quinoline. Activities of the newly synthesized compounds were estimated by means of Ellman’s method. Compound 6h (IC50 = 3.65 nM) was found to be most active. All obtained novel compounds present comparable activity to that of tacrine towards acetylcholinesterase (AChE) and, simultaneously, lower activity towards butyrylcholinesterase (BChE). Apart from 6a, all synthesized compounds are characterized by a higher affinity for AChE and a lower affinity for BChE in comparison with tacrine. Among all obtained molecules, compound 6h presented the highest selectivity towards inhibition of acetylcholinesterase. Molecular modeling showed that all compounds demonstrated a similar binding mode with AChE and interacted with catalytic and peripheral sites of AChE. Also, a biodistribution study of compound 6a radiolabeled with 99mTc was performed.
Keywords: biological activity; medicinal chemistry; isotopic labeling; drug design; radiopharmaceuticals biological activity; medicinal chemistry; isotopic labeling; drug design; radiopharmaceuticals
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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MDPI and ACS Style

Szymański, P.; Lázničková, A.; Lázniček, M.; Bajda, M.; Malawska, B.; Markowicz, M.; Mikiciuk-Olasik, E. 2,3-Dihydro-1H-cyclopenta[b]quinoline Derivatives as Acetylcholinesterase Inhibitors—Synthesis, Radiolabeling and Biodistribution. Int. J. Mol. Sci. 2012, 13, 10067-10090.

AMA Style

Szymański P, Lázničková A, Lázniček M, Bajda M, Malawska B, Markowicz M, Mikiciuk-Olasik E. 2,3-Dihydro-1H-cyclopenta[b]quinoline Derivatives as Acetylcholinesterase Inhibitors—Synthesis, Radiolabeling and Biodistribution. International Journal of Molecular Sciences. 2012; 13(8):10067-10090.

Chicago/Turabian Style

Szymański, Paweł; Lázničková, Alice; Lázniček, Milan; Bajda, Marek; Malawska, Barbara; Markowicz, Magdalena; Mikiciuk-Olasik, Elżbieta. 2012. "2,3-Dihydro-1H-cyclopenta[b]quinoline Derivatives as Acetylcholinesterase Inhibitors—Synthesis, Radiolabeling and Biodistribution." Int. J. Mol. Sci. 13, no. 8: 10067-10090.



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