Synthesis and In-Silico Analysis of Novel Tetrahydroquinolines and Their Antioxidant Activity

Abstract

Within the area of study of neurodegenerative diseases, particularly Alzheimer’s disease (AD), this research focused on the synthesis and evaluation of novel tetrahydroquinoline (THQ) derivatives with potential antioxidant activity. The toluidine N-propargylation synthesis protocol was optimized, achieving a significant increase in yield by using sodium carbonate and reaction temperature variation. Subsequently, four THQ compounds with alkene variation were successfully synthesized, including some which had not been previously reported in the literature. The synthesized compounds were characterized by nuclear magnetic resonance (NMR), mass spectrometry, and infrared spectroscopy (IR), which confirmed their structures and purity. In silico analyses performed with SwissADME and OSIRIS Property Explorer indicated that most of the compounds exhibited excellent drug-like characteristics and favorable pharmacokinetic profiles. Antioxidant evaluation was performed using DPPH and ABTS assays, in which all compounds demonstrated excellent antioxidant capacity, with EC50 values below 10 μg/mL in the ABTS assay, significantly outperforming the ascorbic acid control (EC50 = 35 μg/mL). The results suggest that the predominant radical-scavenging mechanism is single electron transfer (SET). This study provides a solid foundation for further investigations into the potential of THQs’ derivatives as antioxidants, and potential cholinesterase inhibitors in the context of neurodegenerative diseases such as Alzheimer’s. As a future projection, an enzymatic evaluation, including regarding mechanisms of action and the exploration of a hybrid synthesis of THQ/triazole, is proposed based on these promising results.

Keywords

• THQ
• synthesis
• povarov reaction
• antioxidant