Design, synthesis, spectroscopic characterization, computational analysis, and in vitro α-amylase and α-glucosidase evaluation of 3-aminopyridin-2(1H)-one based novel monothiooxamides and 1,3,4-thiadiazoles

Abstract

Due to the global growth in the incidence of diabetes mellitus throughout the world, the urgency of the search for new safe and effective inhibitors of α-amylase and α-glucosidase is...

Synthesis, Computational Study, and In Vitro α-Glucosidase Inhibitory Action of 1,3,4-Thiadiazole Derivatives of 3-Aminopyridin-2(1H)-ones

“…In our recently published work [ 24 ], three laboratory-accessible derivatives of 3-aminopyridin-2(1 H )-one 1a – c were used to obtain mono-thioxamide derivatives 3 , 4a – c .…”

“…Subsequently, through the cyclization of thiohydrazides 4a – c using 2-chloroacetyl chloride and succinic anhydride, the first derivatives of 1,3,4-thiadiazole 5 and 6a – c with a pyridone framework were obtained ( Scheme 1 ) [ 24 ].…”

“…The synthesized derivatives of 1,3,4-thiadiazoles 5 and 6a – c showed sufficiently high antidiabetic activity in vitro against α -amylase and α -glucosidase enzymes, as well as low IC 50 values. Furthermore, it was found that all 12 synthesized compounds, 3 ( a – c ), 4 ( a – c ), 5 ( a – c ), 6 ( a – c ), exhibited not only low cytotoxicity but also pronounced cytoprotective properties in the cytotoxicity assay (MTT test) [ 24 ].…”

“…The analysis of the “structure–activity” relationship showed that elongating the acidic linker from propionic acid to butanoic acid (compound 7′a – c ) for the starting structures 5′a – c [ 24 ] not only significantly increased the degree of inhibition (from 36% to 95%), but also decreased the IC 50 value (down to 6.7 µg/mL for 7′b ). The introduction of an aromatic acid linker also led to an increase in the degree of inhibition (up to 95% for 9′b ) and a decrease in the IC 50 value (to a minimum of 3.66 µg/mL for 9′b ).…”

New 1,3,4-Thiadiazole Derivatives as α-Glucosidase Inhibitors: Design, Synthesis, DFT, ADME, and In Vitro Enzymatic Studies

“…Previous 1,3,4-thiadiazole − and Schiff base − derivatives (Figure ) have shown various biological activities, but in current research, we will design novel routes for the synthesis of 2-hydrazine-5-(4-nitrophenyl)-1,3,4-thiadiazole-bearing Schiff base derivatives to overcome such issues in the future.…”