Abstract
In this study, the chemical investigation of Tetraena aegyptia (Zygophyllaceae) led to the identification of a new megastigmene derivative, tetraenone A ((2S, 5R, 6R, 7E)-2-hydroxy-5,6-dihydro-β-ionone) (1), along with (3S, 5R, 6S, 7E)-3-hydroxy-5,6-epoxy-5,6-dihydro-β-ionone- (2), 3,4-dihydroxy-cinnamyl alcohol-4-glucoside (3), 3β,19α-dihydroxy-ursan-28-oic acid (4), quinovic acid (5), p-coumaric acid (6), and ferulic acid (7), for the first time. The chemical structures of 1-7 were confirmed by analysis of their 1D and 2D NMR and HRESIMS spectra and by their comparison with the relevant literature. The absolute configurations of 1 and 2 were assigned based on NOESY interactions and ECD spectra. Conformational analysis showed that 1 existed exclusively in one of the two theoretically possible chair conformers with a predominant s-trans configuration for the 3-oxobut-1-en-1-yl group with the ring, while the half-chair conformer had a pseudo-axial hydroxy group that was predominant over the other half-chair conformation. Boat conformations were not among the most stable conformations, and the s-trans isomerism was in favor of s-cis configuration. In silico investigation revealed that 1 and 2 had more favorable binding interactions with M(pro) rather than with TMPRSS2. Accordingly, molecular dynamic simulations were performed on the complexes of compounds 1 and 2 with M(pro) to explore the stability of their interaction with the target protein structure. Compounds 1 and 2 might offer a possible starting point for developing covalent inhibitors of M(pro) of SARS-CoV-2.