17917-62-3Relevant academic research and scientific papers
α-Glucosidase Inhibition, Antioxidant and Docking Studies of Hydroxycoumarins and their Mono and Bis O-alkylated/acetylated Analogs
Singh, Parvesh,Ngcoya, Nomandla,Mopuri, Ramgopal,Kerru, Nagaraju,Manhas, Neha,Ebenezer, Oluwakemi,Islam, Md. Shahidul
, p. 127 - 135 (2018/03/21)
Background: Diabetes Mellitus (DM) is a complex metabolic disease illustrated by abnormally high levels of plasma glucose or hyperglycaemia. Accordingly, several α-glucosidase inhibitors have been developed for the treatment of diabetes and other degenerative disorders. While, a coumarin ring has the privilege to represent numerous natural and synthetic compounds with a wide spectrum of biological activities e.g. anti-cancer, anti-HIV, anti-viral, anti-malarial, anti-microbial, anti-convulsant, anti-hypertensive properties. Besides this, coumarins have also shown potential to inhibit α-glucosidase leading to a generation of new promising antidiabetic agents. However, the testing of O-substituted coumarins for α-glucosidase inhibition has evaded the attention of medicinal chemists. Methods: For O-alkylation/acetylation reactions, the hydroxyl coumarins (A-B) initially activated by K2 CO3 in dry DMF were reacted with variedly substituted haloalkanes at room temperature under nitrogen. The synthesized compounds were tested for their α-glucosidase (from Saccharomyces cerevisiae) inhibitory activity and anti-oxidant activity using DPPH radical scavenging activity. In silico docking simulations were conducted using CDocker module in DS (Accelrys) to explore the binding modes of the representative compounds in the catalytic site of α-glucosidase. Results: All the coumarin analogues (A1, B1, A2-A10, B2-B8) including their precursors (A-B) were evaluated for their in vitro α-glucosidase inhibition using acarbose as a standard inhibitor. All the mono O-alkylated coumarins (except A1) showed significant (p 50 values ranging between 11.084±0.117 to 145.24± 29.22 μg/mL. Compound 7-(benzyloxy)-4, 5-dimethyl-2H-chromen-2-one (A9) bearing a benzyl group (Ph-CH2 -) at position 7 showed a remarkable (p 50 = 11.084±0.117 μg/mL), almost four-fold more than acarbose (IC50 = 40.578±5.999 μg/mL). The introduction of –NO2 group dramatically improved the anti-oxidant activity of coumarin, while the O-alkylation/acetylation decreased the activity. Conclusion: The present study describes the synthesis of functionalized coumarins and their evaluation for α-glucosidase inhibition and antioxidant activity under in vitro conditions. Based on IC50 data, the mono O-alkylated coumarins were observed to be stronger inhibitors of α-glucosidase with respect to their bis O-alkylated analogues. Coumarin (A9) bearing O-benzyloxy group displayed the strongest α-glucosidase inhibition, even higher than the standard inhibitor acarbose. The coumarin (A10) bearing –NO2 group showed the highest anti-oxidant activity amongst the synthesized compounds, almost comparable to the ascorbic acid. Finally, in silico docking simulations revealed the role of hydrogen bonding and hydrophobic forces in locking the compounds in catalytic site of α-glucosidase.
Synthesis and antioxidant activities of novel 4-Schiff base-7-benzyloxy- coumarin derivatives
Zhang, Ye,Zou, Biqun,Chen, Zhenfeng,Pan, Yingming,Wang, Hengshan,Liang, Hong,Yi, Xianghui
experimental part, p. 6811 - 6815 (2011/12/22)
4-Schiff base-7-benzyloxy-coumarins 5a1-5h2 and its derivative 6 were designed and synthesized based on the 7-benzyloxy-coumarin structure as novel antioxidants. The in vitro antioxidant activities screening revealed that 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activities of compounds 5b1, 5d1, 5f1, 5f2, 5g1 and 5g2, and 2,2′-azinobis-(3- ethylbenzthiazoline-6-sulfonate) cation (ABTS+) radical scavenging activities of compounds 5a1, 5b1, 5c1, 5c 2, 5d1, 5e1, 5e2, 5f2, 5g1, 5g2 and 5h1 were better than that of the commercial antioxidant butylated hydroxytoluene (BHT), while the superoxide anion radical scavenging activities of 5a2 and 5g2 were stronger than that of the commercial antioxidant butylated hydroxyanisole (BHA), and the hydroxyl radical scavenging activity of 5e1 was much better than that of the common antioxidant ascorbic acid.
