Adamantane-substituted guanylhydrazones: novel inhibitors of butyrylcholinesterase

Bioorganic Chemistry
Marina SekutorInes Primožič

Abstract

A series of novel adamantane-substituted guanylhydrazones was synthesized and used in a study of inhibitory potential toward butyrylcholinesterase. The experimental results were further supported by using docking studies to examine the behavior of the inhibitors within the active site regions of the enzyme. The enzyme-inhibitor dissociation constants K(i) were determined from Hunter-Downs diagrams using Ellman's method for cholinesterase activity determination. Compounds 2-(N-guanidino)iminoadamantane hydrochloride (1) and 2,4-bis(N,N'-guanidino)iminoadamantane dihydrochloride (2) were found to be the best BChE inhibitors and their affinities for the enzyme active site were about five times higher compared to the enzyme peripheral site. The strongest interaction observed in complexes obtained by docking studies was the H-bond between the guanidine and the carboxylate of Glu199 and the second guanidine group in bisguanidine compounds was stabilized with additional H-bonds.

References

Jul 1, 1975·Journal of Medicinal Chemistry·K AigamiA Takatsuki
Nov 15, 1992·Proceedings of the National Academy of Sciences of the United States of America·M HarelI Silman
Jan 1, 1994·Annual Review of Pharmacology and Toxicology·P Taylor, Z Radić
Aug 16, 1996·Journal of Medicinal Chemistry·N KolocourisE De Clercq
Oct 4, 2002·Il Farmaco·Andrzej OrzeszkoBohdan J Starościak
Mar 18, 2003·Bioorganic & Medicinal Chemistry Letters·Takeshi MasudaTakeshi Honda
May 16, 2003·Journal of Medicinal Chemistry·Jarmila KrálováVladimír Král
Jul 2, 2003·European Journal of Medicinal Chemistry·B MasereelD Laeckmann
Jul 1, 1961·Biochemical Pharmacology·G L ELLMANR M FEATHER-STONE
May 15, 1964·Science·W L DAVIESC E HOFFMANN
Mar 23, 2005·Bioorganic & Medicinal Chemistry·Grigoris ZoidisRicardo Felix
Aug 8, 2007·Bioorganic & Medicinal Chemistry·Sultan DarveshEarl Martin
Feb 20, 2008·Journal of Medicinal Chemistry·Ioannis PapanastasiouJohn M Kelly
Apr 29, 2009·Journal of Computational Chemistry·Garrett M MorrisArthur J Olson
Apr 30, 2010·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Mohamed A Al-OmarAli A El-Emam
Dec 24, 2010·The Journal of Physical Chemistry. B·Xi ChenChang-Guo Zhan
Mar 1, 2011·European Journal of Medicinal Chemistry·Joe LiuRachel Codd

❮ Previous
Next ❯

Citations

Feb 11, 2020·Current Pharmaceutical Design·Vasiliki PardaliGrigoris Zoidis

❮ Previous
Next ❯

Related Concepts

Related Feeds

Antifungals

An antifungal, also known as an antimycotic medication, is a pharmaceutical fungicide or fungistatic used to treat and prevent mycosis such as athlete's foot, ringworm, candidiasis, cryptococcal meningitis, and others. Discover the latest research on antifungals here.

Antivirals

Antivirals are medications that are used specifically for treating viral infections. Discover the latest research on antivirals here.

Antivirals (ASM)

Antivirals are medications that are used specifically for treating viral infections. Discover the latest research on antivirals here.

Antifungals (ASM)

An antifungal, also known as an antimycotic medication, is a pharmaceutical fungicide or fungistatic used to treat and prevent mycosis such as athlete's foot, ringworm, candidiasis, cryptococcal meningitis, and others. Discover the latest research on antifungals here.