Bioevaluation of synthetic pyridones as dual inhibitors of α‐amylase and α‐glucosidase enzymes and potential antioxidants

Abstract

Herein, a library of novel pyridone derivatives 1-34 was designed, synthesized, and evaluated for α-amylase and α-glucosidase inhibitory as well as antioxidant activities. Pyridone derivatives 1-34 were synthesized via a one-pot multicomponent reaction of variously substituted aromatic aldehydes, acetophenone, ethyl cyanoacetate, and ammonium acetate in absolute ethanol. Synthetic compounds 1-34 were structurally characterized by different spectroscopic techniques. Most of the tested compounds showed more promising inhibition potential than the standard acarbose (IC 50 = 14.87 ± 0.16 µM) but compounds 13 and 12 were found to be the most potent compounds with IC 50 values of 9.20 ± 0.14 µM and 3.05 ± 0.18 µM against α-amylase and α-glucosidase enzymes, respectively. Compounds 1-34 also displayed moderate antioxidant potential in the range of IC 50 = 96.50 ± 0.45 to 189.98 ± 1.00 µM in comparison to the control butylated hydroxytoluene (BHT) (IC 50 = 66.50 ± 0.36 µM), in DPPH radical scavenging activities. Additionally, all synthetic derivatives were subjected to a molecular docking study to investigate the interaction details of compounds 1-34 (ligands) with the active site of enzymes (receptors). These results indicate that the newly synthesized pyridone class may serve as promising lead candidates for controlling diabetes mellitus and as antioxidants.

Discovery of Phthalimide‐1,2,3‐triazole‐N‐phenylacetamide Hybrids as Potent α‐Glucosidase Inhibitors: Design, Synthesis, ADMET Prediction, and in vitro and in silico Enzymatic Evaluations

“…Many synthetic and natural derivatives with inhibitory effects on α-glucosidase have been reported. [7][8][9][10][11][12][13][14] Several series of synthetic derivatives such as compounds A-B with high inhibitory activity against α-glucosidase have been synthesized, which have a phthalimide core (Figure 1). [15,16] Phthalimide is a nitrogen-containing heterocycle that has a particular importance in the design of new bioactive compounds in medicinal chemistry.…”

“…Many synthetic and natural derivatives with inhibitory effects on α‐glucosidase have been reported [7–14] . Several series of synthetic derivatives such as compounds A – B with high inhibitory activity against α‐glucosidase have been synthesized, which have a phthalimide core (Figure 1).…”

“…13 C NMR (101 MHz, DMSO) δ 167.82, 164.31, 142.52, 136.34, 135.07, 133.18, 132.05, 129.73, 125.32, 123.71, 119.63, 52.62, 33.38, 20.91 ppm. Anal.…”

Simple and Efficient Synthesis of Highly Functional 2-Oxonicotino­nitriles from 2-Chloronicotinonitriles

“…There are -amylase and -glucosidase enzyme inhibitors, 16 EGFRWT and EGFRT790M inhibitors, 17 PIM-1/2 kinase inhibitors, 18 Mcl-1 inhibitors, 19 DNA gyrase active inhibitors, 20,21 potential inhibitors against Alzheimer's dis-ease, 4 and anticancer agents with dual VEGFR-2/HER-2 inhibitory activity. 22 They also exhibit antioxidant, 16,17 neuroprotective, 23 anticancer, 3,24 anti-inflammatory, antipyretic and ulcerogenic, 25 antimicrobial, 21,26 antifungal (antibiofilm), 20 and antiproliferative activities 27 and can be used as drugs for the treatment of autoimmune diseases and as novel neuroregulators. 28 Milrinone, olprinone, and their other analogues containing a fragment of 2-oxo-1,2-dihydropyridine-3-carbonitrile are used as cardiotonic drugs for the treatment of heart failure.…”

“…9,[12][13][14][15] 2-Oxonicotinonitrile core is the main structural unit in various drugs and constantly attracts the attention of researchers due to its extremely diverse biological properties. There are -amylase and -glucosidase enzyme inhibitors, 16 EGFRWT and EGFRT790M inhibitors, 17 PIM-1/2 kinase inhibitors, 18 Mcl-1 inhibitors, 19 DNA gyrase active inhibitors, 20,21 potential inhibitors against Alzheimer's dis-ease, 4 and anticancer agents with dual VEGFR-2/HER-2 inhibitory activity. 22 They also exhibit antioxidant, 16,17 neuroprotective, 23 anticancer, 3,24 anti-inflammatory, antipyretic and ulcerogenic, 25 antimicrobial, 21,26 antifungal (antibiofilm), 20 and antiproliferative activities 27 and can be used as drugs for the treatment of autoimmune diseases and as novel neuroregulators.…”