Protein tyrosine phosphatase 1B (PTP1B) inhibitors as potential anti-diabetes agents: patent review (2015-2018)

Hussain, Hidayat; Green, Ivan R.; Abbas, Ghulam; Адекенов, С. М.; Hussain, Wahid; Ali, Iftikhar

doi:10.1080/13543776.2019.1655542

Cited by 63 publications

(37 citation statements)

References 47 publications

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“…Extensive research has demonstrated that natural oleanane-type pentacyclic triterpenes display potent inhibitory activity and selectivity against PTP1B [ 17 , 18 , 19 , 20 , 21 ]. Maslinic acid [ 22 , 23 ], oleanolic acid [ 24 , 25 , 26 ] and celastrol [ 27 , 28 , 29 ] are the most representative examples of this type of inhibitors.…”

Section: Introductionmentioning

confidence: 99%

Indole- and Pyrazole-Glycyrrhetinic Acid Derivatives as PTP1B Inhibitors: Synthesis, In Vitro and In Silico Studies

et al. 2021

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Regulating insulin and leptin levels using a protein tyrosine phosphatase 1B (PTP1B) inhibitor is an attractive strategy to treat diabetes and obesity. Glycyrrhetinic acid (GA), a triterpenoid, may weakly inhibit this enzyme. Nonetheless, semisynthetic derivatives of GA have not been developed as PTP1B inhibitors to date. Herein we describe the synthesis and evaluation of two series of indole- and N-phenylpyrazole-GA derivatives (4a–f and 5a–f). We measured their inhibitory activity and enzyme kinetics against PTP1B using p-nitrophenylphosphate (pNPP) assay. GA derivatives bearing substituted indoles or N-phenylpyrazoles fused to their A-ring showed a 50% inhibitory concentration for PTP1B in a range from 2.5 to 10.1 µM. The trifluoromethyl derivative of indole-GA (4f) exhibited non-competitive inhibition of PTP1B as well as higher potency (IC50 = 2.5 µM) than that of positive controls ursolic acid (IC50 = 5.6 µM), claramine (IC50 = 13.7 µM) and suramin (IC50 = 4.1 µM). Finally, docking and molecular dynamics simulations provided the theoretical basis for the favorable activity of the designed compounds.

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Section: Introductionmentioning

confidence: 99%

Indole- and Pyrazole-Glycyrrhetinic Acid Derivatives as PTP1B Inhibitors: Synthesis, In Vitro and In Silico Studies

et al. 2021

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“…The improvement in insulin sensitivity is a key therapeutic strategy in T2DM. Protein tyrosine phosphatase 1B (PTP1B) inhibitors improve the insulin receptor sensitivity and, in the latter years, targeting PTP1B inhibitors is being considered an attractive target to treat T2DM (131). Binding of type 1 insulinlike growth factor (IGF-1) to its tetrameric receptor induces the auto-phosphorylation of the receptor, the downstream activation of protein kinase B (PKB) and mitogen-activated protein kinases (MAPK) pathways triggering the GLUT4 transporter translocation to the plasma membrane (132).…”

Section: Enhance Insulin Activity Via Protein Tyrosine Phosphatase 1b Inhibitionmentioning

confidence: 99%

Phytochemicals as Potential Epidrugs in Type 2 Diabetes Mellitus

et al. 2021

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Type 2 diabetes Mellitus (T2DM) prevalence has significantly increased worldwide in recent years due to population age, obesity, and modern sedentary lifestyles. The projections estimate that 439 million people will be diabetic in 2030. T2DM is characterized by an impaired β-pancreatic cell function and insulin secretion, hyperglycemia and insulin resistance, and recently the epigenetic regulation of β-pancreatic cells differentiation has been underlined as being involved. It is currently known that several bioactive molecules, widely abundant in plants used as food or infusions, have a key role in histone modification and DNA methylation, and constituted potential epidrugs candidates against T2DM. In this sense, in this review the epigenetic mechanisms involved in T2DM and protein targets are reviewed, with special focus in studies addressing the potential use of phytochemicals as epidrugs that prevent and/or control T2DM in vivo and in vitro. As main findings, and although some controversial results have been found, bioactive molecules with epigenetic regulatory function, appear to be a potential replacement/complementary therapy of pharmacological hypoglycemic drugs, with minimal side effects. Indeed, natural epidrugs have shown to prevent or delay the T2DM development and the morbidity associated to dysfunction of blood vessels, eyes and kidneys due to sustained hyperglycemia in T2DM patients.

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“…Protein tyrosine phosphatase 1B (PTP1B) is a non-trans membranous protein that acts as a major negative regulator of insulin signaling pathways, thereby mediating insulin resistance ( Haj et al, 2003 ; Cho, 2013 ; Abdelsalam et al, 2019 ; Hussain et al, 2019 ). The protein tyrosine phosphatases (PTPs) constitute a family of closely related key regulatory enzymes that dephosphorylate phosphotyrosine residues in their protein substrates ( Barford, 1996 ; Alonso et al, 2004 ; Bialy and Waldmann, 2005 ).…”

Section: Introductionmentioning

confidence: 99%

Evaluation of the Hypoglycemic Activity of Morchella conica by Targeting Protein Tyrosine Phosphatase 1B

et al. 2021

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Morchella conica (M. conica) Pers. is one of six wild edible mushrooms that are widely used by Asian and European countries for their nutritional value. The present study assessed the anti-diabetic potential of M. conica methanolic extract (100 mg/kg body weight) on streptozotocin (STZ)-induced diabetic mice. STZ was used in a single dose of 65 mg/kg to establish diabetic models. Body weights, water/food intake and fasting blood glucose levels were measured. Histopathological analysis of the pancreas and liver were performed to evaluate STZ-induced tissue injuries. In addition, in vitro assays such as α-amylase and protein tyrosine phosphatase 1B (PTP1B) inhibitory, antiglycation, antioxidant and cytotoxicity were performed. The in vitro study indicated potent PTP1B inhibitory potential of M. conica with an IC50 value of 26.5 μg/ml as compared to the positive control, oleanolic acid (IC50 36.2 μg/ml). In vivo investigation showed a gradual decrease in blood sugar level in M. conica-treated mice (132 mg/dl) at a concentration of 100 mg/kg as compared to diabetic mice (346 mg/dl). The extract positively improved liver and kidney damages as were shown by their serum glutamic pyruvic transaminase, serum glutamic oxaloacetate, alkaline phosphatase, serum creatinine and urea levels. Histopathological analysis revealed slight liver and pancreas improvement of mice treated with extract. Cytotoxicity assays displayed lower IC50 values. Based on the present results of the study, it may be inferred that M. conica are rich in bioactive compounds responsible for antidiabetic activity and this mushroom may be a potential source of antidiabetic drug. However, further studies are required in terms of isolation of bioactive compounds to validate the observed results.

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Protein tyrosine phosphatase 1B (PTP1B) inhibitors as potential anti-diabetes agents: patent review (2015-2018)

Cited by 63 publications

References 47 publications

Indole- and Pyrazole-Glycyrrhetinic Acid Derivatives as PTP1B Inhibitors: Synthesis, In Vitro and In Silico Studies

Indole- and Pyrazole-Glycyrrhetinic Acid Derivatives as PTP1B Inhibitors: Synthesis, In Vitro and In Silico Studies

Phytochemicals as Potential Epidrugs in Type 2 Diabetes Mellitus

Evaluation of the Hypoglycemic Activity of Morchella conica by Targeting Protein Tyrosine Phosphatase 1B

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