Abstract
A series of fifteen indole derivatives substituted at the C-3 position were synthesized and characterized. The antioxidant activity of all derivatives was investigated by three in vitro antioxidant assays, and the derivative with pyrrolidinedithiocarbamate moiety was the most active as a radical scavenger and Fe3+-Fe2+ reducer. It can be stated that possible hydrogen and electron transfer mechanism is suggested for the quenching of the free radical. Moreover, the indolyl radical stabilization and the presence of unsubstituted indole nitrogen atom are mandatory for the observed antioxidant activity, which strongly depends on the type of the substituent directly connected to the methylene group at the C-3 position. Human red blood cells (RBC) have been used as a cell model to study derivatives interaction with the cell membrane. Haemolytic activity and RBC shape transformation were observed for certain derivatives in a concentration-dependent manner. However, most of the derivatives at sublytic concentration showed high cytoprotective activity against oxidative haemolysis induced by 2,2′-azobis(2-methylpropionamidine) dihydrochloride (AAPH). The cytoprotective properties of derivatives can be explained mostly due to their interactions with the RBC membrane components. Taking together, theoretical estimations and experimental data confirm the beneficial interactions between the selected C-3 substituted indole derivatives and the RBC membrane under oxidative stress conditions. These results encourage us to further structural optimization of C-3 substituted indole derivatives as potent antioxidant compounds.
Highlights
A series of fifteen indole derivatives substituted at the C-3 position were synthesized and characterized
Our results suggest that the mechanism of DPPH radical scavenging by active gramine derivatives could be explained as the indole rings initial hydrogen or electron abstraction
Different functional groups at the methylene group at the C-3 position of the indole nucleus have been shown to modulate the antioxidant ability of newly synthesized derivatives
Summary
A series of fifteen indole derivatives substituted at the C-3 position were synthesized and characterized. Theoretical estimations and experimental data confirm the beneficial interactions between the selected C-3 substituted indole derivatives and the RBC membrane under oxidative stress conditions. These results encourage us to further structural optimization of C-3 substituted indole derivatives as potent antioxidant compounds. Gramine [3-(dimethylaminomethyl)indole] [1] is the main indole-alkaloid present in barley (Hordeum vulgare L.) It is characterized by broad physiological activity; it is used to synthesize new compounds with multifaceted therapeutic properties compared with starting molecule, including antibacterial, antiviral, antitumor, and antioxidant p roperties. conjugates and gramine-triazole conjugates are much more active than gramine as cytoprotective compounds against in vitro induced oxidative damage human red blood cells (RBC)
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