Identification of 1,3,4-Thiadiazolyl-Containing Thiazolidine-2,4-dione Derivatives as Novel PTP1B Inhibitors with Antidiabetic Activity

Abstract

Forty-one 1,3,4-thiadiazolyl-containing thiazolidine-2,4dione derivatives (MY1−41) were designed and synthesized as protein tyrosine phosphatase 1B (PTP1B) inhibitors with activity against diabetes mellitus (DM). All synthesized compounds (MY1−41) presented potential PTP1B inhibitory activities, with half-maximal inhibitory concentration (IC 50 ) values ranging from 0.41 ± 0.05 to 4.68 ± 0.61 μM, compared with that of the positive control lithocholic acid (IC 50 = 9.62 ± 0.14 μM). The most potent compound, MY17 (IC 50 = 0.41 ± 0.05 μM), was a reversible, noncompetitive inhibitor of PTP1B. Circular dichroism spectroscopy and molecular docking were employed to analyze the binding interaction between MY17 and PTP1B. In HepG2 cells, MY17 treatment could alleviate palmitic acid (PA)-induced insulin resistance by upregulating the expression of phosphorylated insulin receptor substrate and protein kinase B. In vivo, oral administration of MY17 could reduce the fasting blood glucose level and improve glucose tolerance and dyslipidemia in mice suffering from DM.

Inhibition mechanism investigation of quercetagetin as a potential tyrosinase inhibitor

“…To the 3.0 mL of tyrosinase solution, 1 μL of quercetagetin was added by titration method ( Li et al, 2024a ; Min et al, 2024 ). The mixture was measured fluorescence spectra at excitation of 280 nm.…”

Honokiol as an α-glucosidase inhibitor

“…Type 2 diabetes mellitus (T2DM) is a growing health concern with increased prevalence ( Xu et al, 2020 ; ElSayed et al, 2023 ; Zhou et al, 2023 ). Now, T2DM has become a significant global health issue ( Hu et al, 2024 ; Li et al, 2024 ). Epidemiological trends indicate that the prevalence of diabetes could reach an alarming 643 million individuals worldwide by 2030 ( Song et al, 2022 ; Lin et al, 2023 ).…”

Water decoction of Pericarpium citri reticulatae and Amomi fructus ameliorates alcohol-induced liver disease involved in the modulation of gut microbiota and TLR4/NF-κB pathway

“…Over the past few decades, numerous natural products and their derivatives have been shown to exhibit excellent biological activities against diabetes and liver diseases ( Hu et al, 2024 ; Li et al, 2024 ). In particular, several natural products have been used in various traditional practices to prevent and treat ALD ( Zhang et al, 2021a ; Sun et al, 2023 ) owing to their minimal toxicity and comprehensive efficacy.…”