TY - JOUR

T1 - Laser-induced twisting of phosphorus functionalized thiazolotriazole as a way of cholinesterase activity change

AU - Pankin, Dmitrii

AU - Khokhlova, Anastasia

AU - Kolesnikov, Ilya

AU - Vasileva, Anna

AU - Pilip, Anna

AU - Egorova, Anastasia

AU - Erkhitueva, Elena

AU - Zigel, Vladislav

AU - Gureev, Maxim

AU - Manshina, Alina

N1 - Funding Information: Laser treatment and UV/Vis absorption spectrometry were performed at Center for Optical and Laser Materials Research; NMR studies were carried out at the Magnetic Resonance Research Centre; samples were prepared at Centre for Molecular and Cell Technologies St. Petersburg State University. Publisher Copyright: © 2020 Elsevier B.V. Copyright: Copyright 2020 Elsevier B.V., All rights reserved.

PY - 2021/2/1

Y1 - 2021/2/1

N2 - Herein, the synthesis, design, and the physicochemical characterization of phosphorus functionalized thiazolotriazole (PFT) compound are presented. The PFT tests on the biological activity revealed butyrylcholinesterase inhibition that was confirmed and explained with molecular docking studies. The pronounced reduction of optical density and biological activity was found as a result of irradiation of the PFT water solution with laser beam at wavelength 266 nm. The observed phenomenon was explained on the base of molecular dynamics, docking, and density functional theory modeling by the formation of PFT conformers via laser-induced phosphonate group twisting. The reorganization of the PFT geometry was found to be a reason of butyrylcholinesterase inhibition mechanism change and the site-specificity loss. These results demonstrate that PFT combines photoswitching and bioactive properties in one molecule that makes it promising as a molecular basis for the further design of bioactive substances with photosensitive properties based on the mechanism of the phosphonate group phototwisting.

AB - Herein, the synthesis, design, and the physicochemical characterization of phosphorus functionalized thiazolotriazole (PFT) compound are presented. The PFT tests on the biological activity revealed butyrylcholinesterase inhibition that was confirmed and explained with molecular docking studies. The pronounced reduction of optical density and biological activity was found as a result of irradiation of the PFT water solution with laser beam at wavelength 266 nm. The observed phenomenon was explained on the base of molecular dynamics, docking, and density functional theory modeling by the formation of PFT conformers via laser-induced phosphonate group twisting. The reorganization of the PFT geometry was found to be a reason of butyrylcholinesterase inhibition mechanism change and the site-specificity loss. These results demonstrate that PFT combines photoswitching and bioactive properties in one molecule that makes it promising as a molecular basis for the further design of bioactive substances with photosensitive properties based on the mechanism of the phosphonate group phototwisting.

KW - Biological activity

KW - Butyrylcholinesterase inhibition

KW - Laser chemistry

KW - Laser-induced processes

KW - Phosphonates

KW - PHOSPHONATES

KW - PROTEIN

KW - ANTITUBERCULOSIS ACTIVITY

KW - BIOLOGICAL EVALUATION

KW - ANTIBACTERIAL

KW - ANTIFUNGAL

KW - LIGAND

UR - http://www.scopus.com/inward/record.url?scp=85092000075&partnerID=8YFLogxK

U2 - 10.1016/j.saa.2020.118979

DO - 10.1016/j.saa.2020.118979

M3 - Article

AN - SCOPUS:85092000075

VL - 246

JO - SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY

JF - SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY

SN - 1386-1425

M1 - 118979

ER -