One-Pot Multicomponent Synthesis and Bioevaluation of Tetrahydroquinoline Derivatives as Potential Antioxidants, α-Amylase Enzyme Inhibitors, Anti-Cancerous and Anti-Inflammatory Agents

Abstract

Mankind has always suffered from multiple diseases. Therefore, there has been a rigorous need in the field of medicinal chemistry for the design and discovery of new and potent molecular entities. In this work, thirteen tetrahydroquinoline derivatives were synthesized and evaluated biologically for their antioxidant, α-amylase enzyme inhibitory, anti-proliferative and anti-inflammatory activities. SF8 showed the lowest IC50 of 29.19 ± 0.25 µg/mL by scavenging DPPH free radicals. SF5 showed significant antioxidant activity in total antioxidant capacity (TAC) and total reducing power (TRP) assays. SF5 and SF9 showed the maximum inhibition of α-amylase enzyme i.e., 97.47% and 89.93%, respectively, at 200 µg/mL concentration. Five compounds were shortlisted to determine their anti-proliferative potential against Hep-2C cells. The study was conducted for 24, 48 and 72 h. SF8 showed significant results, having an IC50 value of 11.9 ± 1.04 µM at 72 h when compared with standard cisplatin (IC50 value of 14.6 ± 1.01 µM). An in vitro nitric oxide (NO) assay was performed to select compounds for in vivo anti-inflammatory activity evaluation. SF13 scavenged the NO level to a maximum of 85% at 50 µM concentration, followed by SF1 and SF2. Based on the NO scavenging assay results, in vivo anti-inflammatory studies were also performed and the results showed significant activity compared to the standard, acetylsalicylic acid (ASA).

Phytochemical analysis and comprehensive evaluation of pharmacological potential of Artemisia brevifolia Wall. ex DC

“…This is based on the fact that reactive oxygen species are the prime mediators for oxidative stress and inflammation. Nitric oxide, an important chemical mediator of oxidation and inflammation, is involved in the regulation of numerous physiological processes but its excessive production brings about deleterious effects ( Farooq et al, 2020 ). It reacts with oxygen under aerobic conditions and generates highly reactive intermediate species, i.e., nitrate, nitrite and peroxynitrite, which can induce oxidative stress.…”

Recent Developments in the Synthesis of N‐Heterocyclic Compounds as α‐Amylase Inhibitors via In‐Vitro and In‐Silico Analysis: Future Drugs for Treating Diabetes

“…All the analogues were obtained in good yield up to 87 % and exhibited better inhibitory potential. Methylpiprezinyl substituted derivative showed maximum inhibition potential IC 50 =17 μM as compared to that of acarbose (IC 50 =38±0.98 μM) [82] …”

“…Methylpiprezinyl substituted derivative showed maximum inhibition potential IC 50 = 17 μM as compared to that of acarbose (IC 50 = 38 � 0.98 μM). [82] Figure 10 explains a comparison between all the most potential derivatives of series 2.6 with acarbose as well as among themselves. The graph shows that compound 88 L has shown excellent inhibition potential among the whole series.…”

Datura stramonium Leaf Extract Exhibits Anti-inflammatory Activity in CCL4-Induced Hepatic Injury Model by Modulating Oxidative Stress Markers and iNOS/Nrf2 Expression

“…The selected extract was also analyzed for its nitric oxide (NO) scavenging potential in murine macrophages using the Griess reagent method reported previously [ 80 ]. The experiment was performed in a 96-well plate, isolated macrophages were seeded at a density of 1 × 10 6 per well, and the plate was kept at 37°C for 24 hr in a 5% CO 2 incubator.…”