Quinoline Derivatives: Promising Antioxidants with Neuroprotective Potential

Abstract

Quinoline has been proposed as a privileged molecular framework in medicinal chemistry. Although by itself it has very few applications, its derivatives have diverse biological activities. In this work, 8536 quinoline derivatives, strategically designed using the CADMA-Chem protocol, are presented. This large chemical space was sampled, analyzed and reduced using selection and elimination scores that combine their properties of bioavailability, toxicity and manufacturability. After applying several filters, 25 derivatives were selected to investigate their acid–base, antioxidant and neuroprotective properties. The antioxidant activity was predicted based on the ionization potential and bond dissociation energies, parameters directly related to the transfer of hydrogen atoms and of a single electron, respectively. These two mechanisms are typically involved in the radical scavenging processes. The antioxidant efficiency was compared with reference compounds, and the most promising antioxidants were found to be more efficient than Trolox but less efficient than ascorbate. In addition, based on molecular docking simulations, some derivatives are expected to act as inhibitors of catechol-O methyltransferase (COMT), acetylcholinesterase (AChE) and monoamine oxidase type B (MAO-B) enzymes. Some structural insights about the compounds were found to enhance or decrease the neuroprotection activity. Based on the results, four quinoline derivatives are proposed as candidates to act as multifunctional antioxidants against Alzheimer’s (AD) and Parkinson’s (PD) diseases.

A comprehensive review on the progress and challenges of tetrahydroisoquinoline derivatives as a promising therapeutic agent to treat Alzheimer's disease

“…Some specific chemical modifications can also be conducted to synthesize multi-targeted THIQ direct ligands. Additional substituents, such as phenolic and quinoline groups, can be integrated into the THIQ analogs to enhance their antioxidant properties [ 136 ].…”

Synthesis, Antioxidant, and Anticancer Studies of New 1,3,4‐Oxadiazole Derivatives Linked to Benzoquinoline

“…On the other hand, quinoline is a nitrogen‐containing heterocyclic ring with significant biological and pharmacological applications [25–27] . Current biological breakthroughs related to quinoline and its derivatives have included antimicrobial, [28] antioxidant, [29] anti‐inflammatory, [30,31] and anti‐Alzheimer [32] . One of the most important biological properties of quinoline is its anticancer activity [33–35] .…”