Design, synthesis and α-glucosidase inhibition study of novel embelin derivatives

Abstract

Embelin is a naturally occurring para-benzoquinone isolated from Embelia ribes (Burm. f.) of the Myrsinaceae family. It was first discovered to have potent inhibitory activity (IC 50 ¼ 4.2 lM) against a-glucosidase in this study. Then, four series of novel embelin derivatives were designed, prepared and evaluated in a-glucosidase inhibition assays. The results show that most of the embelin derivatives synthesised are effective a-glucosidase inhibitors, with IC 50 values at the micromolar level, especially 10d, 12d, and 15d, the IC 50 values of which are 1.8, 3.3, and 3.6 lM, respectively. Structure-activity relationship (SAR) studies suggest that hydroxyl groups in the 2/5-position of para-benzoquinone are very important, and long-chain substituents in the 3-position are highly preferred. Moreover, the inhibition mechanism and kinetics studies reveal that all of 10d, 12d, 15d, and embelin are reversible and mixed-type inhibitors. Furthermore, docking experiments were carried out to study the interactions between 10d and 15d with a-glucosidase.

Antioxidant Properties of Embelin in Cell Culture. Electrochemistry and Theoretical Mechanism of Scavenging. Potential Scavenging of Superoxide Radical through the Cell Membrane

“…Interestingly, the defensive power of embelin against paraquat-incited lung damage was studied in relationship with its antioxidant and anti-inflammatory action. Oxidative stress markers, like malondialdehyde (MDA), antioxidative enzymes, such as superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH Px), inflammatory cytokines, for example interleukin-1β (IL-1β), tumor necrosis factor-α, and IL-6, along with histological examination, and nuclear factor kappa B/mitogen-activated protein kinase (NF-κB/MAPK) gene expression were evaluated in lung tissue [9,10]. Embelin treatment significantly decreased MDA and increased SOD, CAT, and GSH Px.…”

Design and Synthesis of Fluoroquinolone Derivatives as Potent α‐Glucosidase Inhibitors: In Vitro Inhibitory Screening with In Silico Docking Studies

“…Results shows that all compounds 1 – 10 are excellent inhibitors of α‐glucosidase with IC 50 in the range of 45.8–74.5 μ M compared to standard 1‐deoxynojirimycin (DNJ) with an IC 50 value of 425.6 μ M. Study reveals that precursor enoxacin exhibit and IC 50 value of 58.9 μ M while substitution of benzyl group as in compound 1 increases the inhibition potential to a small extent with an IC 50 value of 57.8 μ M. Substitution of chloro at meta and para position as in molecules 5 , bromo at ortho 6 and fluoro at ortho and para position 8 on benzyl further increased the inhibition potentials IC 50 values 52.7, 45.8 and 48.7 μ M. Whereas compounds 2 , 3 , 4 , 7 , 9 and 10 were found to have higher IC 50 values in the range of 59.8‐74.5 μ M. Compound 6 was found to be a most potent inhibitor of α ‐glucosidase with an IC 50 value 45.8 μ M. Studies found that position and nature of substituent group shows effect on inhibition potential [40–43] . It is suggested that little variation in hydrogen bonding between protein active sites and synthetic compounds are responsible for variation in inhibition potential of these compounds against α ‐glucosidase [44–46] .…”

Embelin as Lead Compound for New Neuroserpin Polymerization Inhibitors

“…The synthesis of embelin ( 1a ) and its analogs 1b – 1d started from the common precursor 1,2,4,5-tetramethoxybenzene ( 9 ) [ 34 ] which was subjected to an ortho-metalation reaction in the presence of n -BuLi ( Figure 4 ). To obtain the intermediates 10a , 10d and 10g the ortho-metalation reactions were carried out in presence of hexamethylphosphoramide (HMPA) at −40 °C [ 38 ]. On the contrary, the intermediates 10c and 10b were obtained carrying out the reaction at room temperature and without HMPA [ 39 ].…”