Water-soluble betaines and amines based on thiacalix[4]arene scaffold as new cholinesterase inhibitors

Pavel L Padnya; Egor E Bayarashov; Irina V Zueva; Sofya V Lushchekina; Oksana A Lenina; Vladimir G Evtugyn; Yuri N Osin; Konstantin A Petrov; Ivan I Stoikov

doi:10.1016/j.bioorg.2019.103455

Water-soluble betaines and amines based on thiacalix[4]arene scaffold as new cholinesterase inhibitors

Bioorg Chem. 2020 Jan:94:103455. doi: 10.1016/j.bioorg.2019.103455. Epub 2019 Nov 21.

Authors

Pavel L Padnya¹, Egor E Bayarashov¹, Irina V Zueva², Sofya V Lushchekina³, Oksana A Lenina², Vladimir G Evtugyn⁴, Yuri N Osin⁴, Konstantin A Petrov², Ivan I Stoikov⁵

Affiliations

¹ A.M. Butlerov Chemical Institute, Kazan Federal University, Kremlevskaya str. 18, Kazan 420008, Russian Federation.
² Arbuzov Institute of Organic and Physical Chemistry, FRC Kazan Scientific Center of RAS, Arbuzov str. 8, Kazan 420088, Russian Federation.
³ N.M. Emanuel Institute of Biochemical Physics of Russian Academy of Sciences, Kosygina str. 4, Moscow 119334, Russian Federation.
⁴ Interdisciplinary Center for Analytical Microscopy, Kazan Federal University, Kremlevskaya str. 18, Kazan 420008, Russian Federation.
⁵ A.M. Butlerov Chemical Institute, Kazan Federal University, Kremlevskaya str. 18, Kazan 420008, Russian Federation. Electronic address: Ivan.Stoikov@mail.ru.

PMID: 31791680
DOI: 10.1016/j.bioorg.2019.103455

Abstract

Novel ammonium and betaine derivatives of p-tert-butylthiacalix[4]arene in cone and 1,3-alternate conformation were synthesized with high yields for the first time. The obtained compounds form in water spherical nanoparticles. It was shown by molecular docking calculations and in vitro experiments that amino and betaine derivatives can inhibit acetylcholinesterase and butyrylcholinesterase on the level of pyridostigmine while the toxicity of the obtained compounds is much lower than that of pyridostigmine.

Keywords: Amines; Betaines; Biological activity; Cholinesterase inhibitors; Thiacalixarenes.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Acetylcholinesterase / metabolism*
Amines / chemistry
Amines / pharmacology*
Betaine / chemistry
Betaine / pharmacology*
Butyrylcholinesterase / metabolism*
Cholinesterase Inhibitors / chemical synthesis
Cholinesterase Inhibitors / chemistry
Cholinesterase Inhibitors / pharmacology*
Dose-Response Relationship, Drug
Humans
Molecular Docking Simulation
Molecular Structure
Phenols / chemistry
Phenols / pharmacology*
Recombinant Proteins / metabolism
Solubility
Structure-Activity Relationship
Sulfides / chemistry
Sulfides / pharmacology*
Water / chemistry

Substances

Amines
Cholinesterase Inhibitors
Phenols
Recombinant Proteins
Sulfides
thiacalix(4)arene
Water
Betaine
Acetylcholinesterase
Butyrylcholinesterase