New phosphinic and phosphonic acids: Synthesis, antidiabetic, anti-Alzheimer, antioxidant activity, DFT study and SARS-CoV-2 inhibition

Abstract

Two new α-aminophosphinic (A) and α-aminophosphonic (B) acids were synthesized through a one-pot three-component reaction with good yields of 89% and 85%, respectively. The NMR and mass spectroscopies have been used to identify the obtained compounds and confirm their structures, while the IR spectroscopy has been used to characterize functional groups and the type of vibrations involved for the studied compounds. Moreover, the examination of the structural properties and the comparison between the theoretical and the experimental results have been performed using DFT/B3LYP/6–31 G (d,p) method. Consequently, the calculated values of the total energy and the energy gap indicate that the (B) is more stable and less reactive than the (A). Also, MEP maps show that oxygen atoms are the probable sites of electrophilic reactions. In this context, the high reactivity of the (A) can be related to the replacement of the (OH) functional group by a hydrogen atom. Further, six in vitro assays have been used to evaluate the antioxidant potential of (A) and (B), which illustrate that both compounds exhibited an excellent activity (e.g., DPPH/IC50(B): 2.42 µg/mL and DPPH/IC50(A): 2.10 µg /mL). The anti-Alzheimer and antidiabetic effects of the studied compounds have been estimated in vitro by evaluating their inhibition of acetylcholinesterase, butyrylcholinesterase and α-glucosidase. The both compounds showed a good inhibitory activity for α-glucosidase (IC50(A): 12.63 and IC50(B): 25.26 µg/mL), and exhibited higher inhibitory activity against butyrylcholinesterase (BChE) than against acetylcholinesterase (AChE) (IC50(A): 36.71±0.95 and IC50(B): 26.56±1.32 µg/mL). Furthermore, the in silico docking study of the inhibitory action of SARS-CoV-2 main protease (Mpro) showed that (A) and (B) have a significant inhibitory action with total energy values of - 96.23 and - 99.99 kcal/mol, respectively.