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BIOMEDICAL PHOTONICS
Meet new photo-pharmacological agents -functionalised phosphonates with Cholinesterase activity
I. Kolesnikov1, D. Mamonova2, D. Pankin1, A. Pilip3, A. Egorova34, and A. Manshina2,*
1 Center for Optical and Laser Materials Research, St. Petersburg State University, St. Petersburg, Russia 2 Institute of Chemistry, St. Petersburg State University, St. Petersburg 198504, Russia 3 St. Petersburg Federal Research Center of the Russian Academy of Sciences (SPC RAS), Scientific Research Centre for Ecological Safety of the Russian Academy of Sciences, St. Petersburg 197110, Russia 4 St. Petersburg State Technological Institute (Technical University), St. Petersburg 190013, Russia
* e-mail: a.manshina@spbu.ru
*
ALT'22
Rapid development of pharmacology generated several breakthrough directions one of which is Photopharmacol-ogy. Nowadays the main players of photopharmacology are 'photoswitch-pharmacore' couples that change biological activity because of light irradiation. The most widely used photoswitchers are azobenzenes and diarylethenes; as phar-macore various antibiotics, Takrin (treatment of Alzheimer's disease) were demonstrated. However, the main practical problem in current strategy is losing of drugs activity after photoswitch introduction. It requires further optimization of the structure for each 'photoswitch-pharmacore' couple. That is why development of new photopharmacological agents combining both functions - bioactivity and ability to change it under light irradiation - is necessary.
Here, we present phosphorylated arylaminomalonates (Fig 1a) and thiazolotriazole (Fig 1b) that demonstrate laser-induced change of bioactivity (butyrylcholinesterase (BChE) inhibition) due to the formation of conformers associated with the phosphonate group twisting [1,2]. We found that laser-induced 3D geometry reorganization of the presented compounds leads to the fundamental change of the inhibition mechanism and loss of site-specificity due to the change of interaction region. It is important to note that arylaminomalonates and thiazolotriazole demonstrate opposite effect to laser irradiation in terms of sign of BChE inhibition change - thiazolotriazole decrease inhibition, while arylaminomalonates increase inhibition as a result of laser irradiation. The uncovered photosensitivity and bioactivity of new phosphorylated phosphonates makes them promising compounds for clinical therapy as photopharmacological agents.
Figure 1. Structures of (a) phosphorylated arylaminomalonates and (b) thiazolotriazole compounds
This work was supported by RSFproject 22-13-00082. Authors are grateful to "Centre for Optical and Laser materials research", Research Park of Saint Petersburg State University for technical support.
[1] D. Pankin, A. Khokhlova, I. Kolesnikov, A. Vasileva, A. Pilip, A. Egorova, E.Erkhitueva, V. Zigel, M. Gureev, A. Manshina, Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy. 246, 118979(2021).
[2] I. Kolesnikov, A. Khokhlova, D. Pankin, A. Pilip, A. Egorova, V. Zigel, M. Gureev, G. Leuchs, A. Manshina, New J. Chem. 45,
15195-15199(2021).
