Multifunctional isoxazolidine derivatives as α-amylase and α-glucosidase inhibitors

Abstract

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Synthesis and characterization of novel isoxazolidine-thiosemicarbazone hybrid derivatives as precursor of unnatural amino acids

“…1H NMR (300 MHz, DMSO-d6) δ 0.77 (d, 3H, J = 6.6 Hz, CH 3 ), 0.80 (d, 3H, J = 6.9 Hz, CH 3 ), 0.83 (d, 3H, J = 6.9 Hz, CH 3 ), 0.92 (m, 1H), 1.28 (m, 2H), 1.40 (m, 1H), 1.53 (m, 2H), 1.67 (d, 1H, J = 11.7 Hz), 1.79 (m, 1H), 1.91 (d, 1H, J = 12.6 Hz), 2.37 (m, 1H), 2.55 (ddd, 1H, J = 12.6 Hz, J = 5.7 Hz, J = 1.5 Hz), 2.65 (s, 3H, NCH 3 ), 3.91 (d, 1H, J = 8.4 Hz), 4.01 (m, 2H), 4.12 (m, 1H), 6.76 (dd, 1H, J = 9 Hz, J = 3 Hz), 6.90 (d, 1H, J = 9 Hz), 7. 40 1 H NMR (300 MHz, DMSO-d6) δ 0.79 (d, 3H, J = 6.9 Hz, CH 3 ), 0.81 (d, 3H, J = 6.9 Hz, CH 3 ), 0.85 (d, 3H, J = 6.6 Hz, CH 3 ), 0.91 (m, 1H), 1.28 (m, 2H), 1.40 (m, 1H), 1.54 (m, 2H), 1.67 (d, 1H, J = 12.9 Hz), 1.79 (m, 1H), 1,89 (d, 1H, J = 12.6 Hz), 2.30 (m, 1H), 2.46 (m, 1H), 2.64 (s, 3H, NCH 3 ), 3.90 (d, 1H, J = 8.7 Hz), 4.06 (m, 3H), 6.41 (s, 2H), 6.94 (d, 2H, J = 8.7 Hz), 7.63 (d, 2H, J = 9 Hz), 7.77 (s, 1H, CH=N), 10.10 (s, 1H, NH); 13 C NMR (75 MHz, DMSO-d6): δ 18.5; 22.2; 22.3; 24.0; 24.2; 25.7; 29.1; 34.1; 34.6; 47.1; 64.9; 67.8; 74.9; 88.5; 114.9; 127.8; 128.2; 139.2; 157.0; 159.3; 172.0. HRMS, (ESI) calcd C 24 H 35 N 5 NaO 4 [M+Na] + : 480.2578, found 480.2581.…”

“…In addition, our research group has been worked for years on the synthesis of enantiopure isoxazolidine derivatives [29][30][31][32][33][34][35][36][37][38]. Some analogues show antimicrobial [31], antioxidant [32] and anti-diabetic [39,40] activities. Likewise, certain derivatives have been used for access to natural and unnatural amino acids [33,36] such as 4-hydroxyisoleucine [41,42] and 4(S)-4-hydroxy-L-ornithine [43].…”

Pharmacodynamic comparison of acarbose tablets in Chinese healthy volunteers under chewing and swallowing conditions

“…It can also competitively bind to α-glucosidase in the small intestine and inhibit the hydrolysis of oligosaccharides and polysaccharides, resulting in a delay of intestinal glucose absorption, thereby controlling blood sugar levels. [4][5][6] Acarbose is effective in treating patients with impaired glucose tolerance, early diabetes and comorbidities of age-related visceral obesity. [7][8][9] It is relatively well-tolerated clinically, although mild gastrointestinal symptoms can occur.…”

“…glucose) and inhibits glycoside hydrolases that are important for carbohydrate digestion. It can also competitively bind to α‐glucosidase in the small intestine and inhibit the hydrolysis of oligosaccharides and polysaccharides, resulting in a delay of intestinal glucose absorption, thereby controlling blood sugar levels 4–6 . Acarbose is effective in treating patients with impaired glucose tolerance, early diabetes and comorbidities of age‐related visceral obesity 7–9 .…”

Synthesis, Structure, Carbohydrate Enzyme Inhibition, Antioxidant Activity, In Silico Drug-Receptor Interactions and Drug-Like Profiling of the 5-Styryl-2-Aminochalcone Hybrids

“…α-Amylase is secreted from the pancreas, and this enzyme is responsible for converting large starch and glycogen molecules into simpler absorbable sugars [ 1 , 5 ] that are, in turn, converted by α-glucosidase into glucose for intestinal absorption [ 6 , 7 ]. Dual inhibition of the activity of intestinal α-glucosidase and pancreatic α-amylase suppresses carbohydrate digestion, in turn, delay glucose uptake leading to reduced blood sugar levels [ 1 , 8 , 9 ]. Glucosidase inhibitors continue to attract considerable interest in medicinal chemistry due to their promising therapeutic potential in the treatment of disorders such as diabetes, human immunodeficiency virus (HIV) infection, metastatic cancer, and lysosomal storage diseases [ 10 ].…”