Synthesis, Characterization, and Evaluation of in vitro Antidiabetic Activity of Novel Pyrrolidine Sulphonamide Derivative

Abstract

Background: Diabetes is a long-term illness characterized by high blood sugar levels. It is estimated that by 2045, there will be nearly 693 million diabetic patients worldwide, with half of the population remaining undiagnosed. Metformin, insulin, sulfonylureas, and thiazolidinediones were related to several risk factors, including hypoglycemia, bone fracture, weight gain, cardiovascular, renal, and other complications. In the present study, we have explored the DPP-IV inhibitors as a new class of antidiabetic drugs. Objectives: The goal of DPP-IV inhibitors is to raise levels of incretins (GLP-1 and GIP), which block glucagon release while boosting insulin secretion, slowing stomach emptying, and reducing blood glucose levels. Methods: A series of derivatives substituted on Oxadiazole of sulfonamide pyrrolidine were produced by reacting 1,2,4-oxadiazol and sulfonyl chloride at room temperature in the presence of ethanol and stirring until the reaction was complete. The compounds were characterized using IR, 1 H NMR, C 13 NMR, mass spectroscopy, elemental analysis, and screened for in vitro assay of DPP-IV inhibition. Results and Discussion: The IC 50 was calculated for compounds B-I, B-V, B-VI, B-XI, and B-XIII that inhibited enzymes significantly, IC 50 values ranging from 19.65 ± 2.60 nM to 11.32 ± 1.59 nM, respectively, and Vildagliptin (4.79±1.66 IC 50 nM) was used as a standard. The most active derivative substituted Oxadiazole of pyrrolidine sulfonamide is B-XI (11.32 ± 1.59 IC 50 nM) among all synthesized compounds. Conclusion: B-XI derivative has shown appreciable DPP-IVinhibitory action. The 1,2,4-oxadiazol-3-yl pyrrolidine-1-sulfonamide derivatives have shown anti-diabetic properties.

Recent insights about pyrrolidine core skeletons in pharmacology

“…Compound 22c could be considered the lead compound for future research. Salve and Jadhav (2021) synthesized novel pyrrolidine sulfonamide derivatives as DPP-IV inhibitors and compared their in vitro antidiabetic effects with those of vildagliptin as a control. Compounds 23a-d showed 56.32%, 44.29%, 49.62%, and 66.32% inhibition, respectively.…”

“…Compounds bearing pyrrolidine scaffolds continue to be utilized as intermediates in drug research and development (R&D) studies for the development of molecules that could be new drug candidates ( Jeelan Basha et al, 2022 ; Bhat et al, 2023a ). Some pyrrolidine derivatives are known to be employed as pharmacophore groups, with some having antibacterial ( Huang et al, 2015 ), antifungal ( Lukowska-Chojnacka et al, 2019 ), antiviral ( Moni et al, 2015 ), antimalarial ( Meyers et al, 2019 ), antitumoral ( Li et al, 2020 ), anti-inflammatory ( Jan et al, 2020 ), anticonvulsant ( Góra et al, 2020 ), and antioxidant ( Hussain et al, 2019 ) activities, while others have diverse enzyme inhibitory effects ( Zhou et al, 2019 ; Salve and Jadhav, 2021 ; Toumi et al, 2021 ; Poyraz et al, 2023a ). In addition, several compounds with essential bioactive characteristics have been reported in the literature that comprise fused or spiropyrrolidine rings ( Łowicki and Przybylski, 2022 ).…”