Meteloxetin (1) Novel Phenolic Amino-Oxetane Cholinesterase Inhibitors from Datura metel Linn and First-Principle Investigations

Meteloxetin (1), a new phenolic amino-oxetane, and eight known new source phenols (2–9) have been bioassay-directed isolated from methanolic extract of Datura metel Linn. Their structures were elucidated through modern spectroscopic data. The plant extract showed the significant inhibition potential against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), and its dichloromethane (DCM) fraction exhibited the remarkable inhibition potentials against AChE with IC50 (inhibition concentration) value 1.32 ± 0.02 µg/ml and BChE with IC50 value 1.13 ± 0.01 µg/ml, when compared with the standard drug eserine (AChE, IC50 0.04 ± 0.01 µg/ml) and galanthamine (BChE, IC50 0.92 ± 0.01 µg/ml). The bioactive DCM fraction was subjected to systematic isolation protocol to isolate the 1–9 compounds, and all were subjected to evaluate their AChE and BChE inhibition potentials. From these isolates, compound 1 showed the effective inhibition potential against BChE with IC50 value 0.84 ± 0.03 µg/ml and excellent inhibition potential against AChE with IC50 value 0.07 ± 0.02 µg/ml. This strong inhibition potential of 1 is due to the presence of amino-oxetane groups in it. The in silico studies indicate that oxetane rings contain high-energy oxygen, which makes it a marvelous pharmacophore with diverse biological potentials. The potent nature of compound 1 has also been evaluated by exploring its electronic properties, molecular electrostatic potential and Hirshfeld analysis by density functional theory.