Synthesis of N-allyl and N-propargyl Tetrahydroquinolines: Evaluation of Antioxidant Activity and Cholinesterase Inhibition in the Context of Neurodegenerative Diseases such as Alzheimer's.

Abstract

In the context of the study of neurodegenerative diseases, particularly Alzheimer's disease (AD), this work focuses on the synthesis of tetrahydroquinolines (THQ) using a previously reported method, with N-allyl and N-propargyl structural variants. The antioxidant activity was evaluated through ABTS and DPPH assays, contributing to the calculation of SC₅₀ (free radical scavenging) through dose-response curves. Similarly, the enzymatic inhibition of AChE (acetyl cholinesterase) and BChE (butyryl cholinesterase) was determined to obtain the IC₅₀ values, framed within the cholinergic hypothesis for AD treatment.

A toxicity analysis was carried out through the in vitro hemolysis assay, demonstrating low toxicity of the evaluated compounds. Additionally, in silico ADME analysis (Swiss ADME tool) predicted a high probability of penetration through the blood-brain barrier (BBB), along with the estimation of relevant parameters regarding their biotransformation and involvement in xenobiotic metabolism.

It is important to highlight that the N-allyl/propargyl-THQs with a methyl substituent showed the highest activity in the different assays, where N-allyl exhibited better efficiency in inhibiting BChE and N-propargyl in AChE. Furthermore, ABTS seems to be more suitable than DPPH for THQ compounds, as DPPH showed low reactivity overall. These findings represent a significant advancement in the development of compounds with potential palliative therapeutic effects for AD, proposing THQs as promising candidates. The future research projection aims to elucidate mechanisms of action and complement with various bioactivity and cytotoxicity assays.