Naslov
Potential of vitamin B6 dioxime analogues to act as cholinesterase ligands

Autori
Gašo Sokač, Dajana ; Zandona, Antonio ; Roca, Sunčica ; Vikić-Topić, Dražen ; Lihtar, Gabriela ; Maraković, Nikola ; Bušić, Valentina ; Kovarik, Zrinka ; Katalinić, Maja

Izvornik
International journal of molecular sciences (1422-0067) 23 (2022), 21; 13388, 18

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
pyridoxal oxime ; dioxime ; AChE ; BChE ; reversible inhibition ; reactivation ; molecular docking ; cytotoxicity

Sažetak
Seven pyridoxal dioxime quaternary salts (1–7)were synthesizedwith the aimof studying their interactions with human acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). The synthesis was achieved by the quaternization of pyridoxal monooxime with substituted 2- bromoacetophenone oximes (phenacyl bromide oximes). All compounds, prepared in good yields (43–76%) and characterized by 1D and 2D NMR spectroscopy, were evaluated as reversible inhibitors of cholinesterase and/or reactivators of enzymes inhibited by toxic organophosphorus compounds. Their potency was compared with that of their monooxime analogues and medically approved oxime HI-6. The obtained pyridoxal dioximes were relatively weak inhibitors for both enzymes (Ki = 100–400 M). The second oxime group in the structure did not improve the binding compared to the monooxime analogues. The same was observed for reactivation of VX-, tabun-, and paraoxon- inhibited AChE and BChE, where no significant efficiency burst was noted. In silico analysis and molecular docking studies connected the kinetic data to the structural features of the tested compound, showing that the low binding affinity and reactivation efficacy may be a consequence of a bulk structure hindering important reactive groups. The tested dioximes were non-toxic to human neuroblastoma cells (SH-SY5Y) and human embryonal kidney cells (HEK293).

Izvorni jezik
Engleski

Znanstvena područja
Kemija, Biologija

POVEZANOST RADA