Synthesis, characterization, crystal structures, and the biological evaluation of 2-phenylthiazole derivatives as cholinesterase inhibitors

Abstract

Four 2-phenylthiazole derivatives are synthesized, characterized, and evaluated as cholinesterase inhibitors. The structures of the 2-phenylthiazole derivatives are confirmed by 1H and 13C nuclear magnetic resonance spectroscopy, single-crystal X-ray diffraction studies, and Hirshfeld surfaces analysis. Hirshfeld surface analysis of the prepared compounds showed C–H···O intermolecular interactions. The cholinesterase inhibition activities of the synthesized compounds are tested by Ellman’s method. [2-(4-Benzyloxyphenyl)-thiazol-4-yl]-(3,5-dimethylpiperidin-1-yl)-methanone showed the best acetylcholinesterase inhibition activity with an IC50 value of 8.86 µM and the best butyrylcholinesterase inhibition activity with an IC50 value of 1.03 µM. A docking study demonstrates that the same compound interacts with the catalytic anionic site and peripheral anionic site of acetylcholinesterase and the catalytic anionic site of butyrylcholinesterase.

Identification of a 2‐phenylthiazole derivative acetylcholinesterase modulator with in vitro antitumor activity in breast cancer cells

“…2‐phenylthiazole derivatives were synthesized and purified as previously reported (Shi et al., 2020). The structures of the 27 compounds are presented in Table S1.…”

“…The compounds A6 were studied for its potential as AChE (from electric eel) and BuChE (from equine serum) inhibitors using the method previously described (Shi et al., 2020).…”

“…Two series of 2‐phenylthiazole derivatives were synthesized in our previous work, including A series, namely 2‐(4‐(benzyloxy) phenyl) thiazole‐4‐formamide compounds and B series, namely 2‐(4‐ methoxyphenyl) thiazole‐4‐formamide compounds (Shi et al., 2020). They were originally designed as acetylcholinesterase inhibitors (AchEIs).…”

“…At the cholinergic synapse, AChE can degrade acetylcholine, terminate the excitatory effect of neurotransmitters on the postsynaptic membrane, and ensure the normal transmission of nerve signals in the body. Traditionally, AchEIs are used in clinical treatment of neurodegenerative disorders (Shi et al., 2020). Besides this classic role, AChE also possess several “nonclassical” functions in nonneuronal cells including regulate cell proliferation, apoptosis, and invasion.…”