Formylchromone Derivatives as a Novel Class of Protein Tyrosine Phosphatase 1B Inhibitors.

Shim, Yi Sup; Kim, Chul; Yoon, Dae; Lee, Keun‐Hyeung; Cho, Hyeongjin

doi:10.1002/chin.200344121

Cited by 4 publications

(9 citation statements)

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“…Appropriately substituted biphenyl, when docked into the PTP1B enzyme, gives satisfactory attachment to the binding sites of PTP1B. This new compound, VMNS2e, exhibited a glucose‐lowering effect in alloxan‐induced diabetic mice, 8 which was comparable to the compounds having the biphenyl moiety reported earlier 1–6 …”

Section: Discussionmentioning

confidence: 66%

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Novel biphenyl compound, VMNS2e, ameliorates streptozotocin‐induced diabetic nephropathy in rats

Kurundkar

Sachan²,

Kodam

et al. 2010

Journal of Diabetes

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Aim: To study the effect of a new biphenyl synthetic compound showing interactions with the active site of protein tyrosine phosphatase 1B by docking and molecular dynamics, VMNS2e in streptozotocin‐induced diabetic nephropathy in rats with various renal function parameters and renal ultrastructure. Methods: Streptozotocin (55 mg/kg)‐induced diabetic rats were orally treated once daily with VMNS2e (30, 60, and 120 mg/kg) for 8 weeks. The body weight and blood glucose levels of the rats were recorded during the study period. After 8 weeks of treatment creatinine clearance, urinary protein, blood urea nitrogen, urinary albumin excretion rate, and insulin levels were measured. An ultrastructure study of the kidney tissue was performed and the glomerular basement membrane thickness was measured. Results: Eight weeks of VMNS2e treatment significantly reduced the fasting blood glucose level, attenuated elevating blood urea nitrogen levels, and reduced glomerular basement membrane thickness. Conclusion: It is concluded that VMNS2e treatment at 30 and 60 mg/kg, when given for 8 weeks, partly ameliorated early diabetic nephropathy in diabetic rats.

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Section: Discussionmentioning

confidence: 66%

“…Biphenyl was selected in our scheme as a pharmacophore, and various biphenyl derivatives were synthesized in our laboratory. A literature survey showed various compounds with anti‐hyperglycemic activity having biphenyl moiety 1–7 …”

Section: Introductionmentioning

confidence: 99%

Novel biphenyl compound, VMNS2e, ameliorates streptozotocin‐induced diabetic nephropathy in rats

Kurundkar

Sachan²,

Kodam

et al. 2010

Journal of Diabetes

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“…Recently, it has been reported that molecules containing biphenyl as pharmacophore exhibited significant PTP 1B inhibition. X-ray crystallographic studies also indicated that molecules containing biphenyl bind to PTP 1B active site and are held in place through weak hydrogen bonding and van der Waals interactions formed within two hydrophobic domains [28][29][30][31][32]. In our present study, biphenyl has been selected as one of the active pharmacophore for inhibition of PTP 1B.…”

Section: Introductionmentioning

confidence: 79%

Accounting of ligand–receptor interactions to explore and design novel architecture for PTP 1B inhibition: a legitimate approach

Malla

Kumar

2012

Journal of Chemometrics

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Computer‐aided drug design was performed on a diverse set of 103 biphenyl derivatives that demonstrated antidiabetic activity by restraining the protein tyrosine phosphatase 1B (PTP 1B) receptor. A four‐point pharmacophore hypothesis using the PHASE module of Schrödinger suite with one hydrogen bond acceptor (A) and three aromatic rings (R) as pharmacophoric features was generated. The hypothesis, ARRR.2, considered the best hypothesis in the present study is characterized by survival score (3.553), cross‐validated r2 (Q2) (0.722), regression coefficient (0.949), Pearson R (0.867), and F value (492.6). The developed pharmacophore model was externally validated by predicting the activity of test set molecules. Docking algorithm combined with the drug–receptor binding free energetic and pharmacokinetic drug profile envisaged a novel concept, which may provide structural insights for the development of potential PTP 1B inhibitors. The study also provided a valid rapport between pharmacophore drug mapping, atom‐based three‐dimensional quantitative structure–activity relationship, molecular docking, sitemap, molecular simulations, and pharmacokinetic prediction approaches demonstrating the trends in activity. The results of these ligand–receptor relationship studies may account to design a legitimate template for the development and optimization of highly selective and potent PTP 1B inhibitors. Copyright © 2012 John Wiley & Sons, Ltd.

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“…A successful 3D-QSAR study was performed to establish relationship between the 3D-pharmacophoric features and PTP 1B inhibitory activity of formylchromane derivatives (8,9). The present 3D-QSAR investigation was performed with the data set of 36 molecules having a well-defined PTP 1B inhibitory activity cited as IC 50 values in lM concentrations.…”

Section: Data Set For Analysismentioning

confidence: 99%

“…It can also be explored to identify and describe important structural requirements of the molecules that are pertinent to optimal biological activity. Recently, various derivatives of formylchromanes were reported that possess remarkably selective PTP 1B inhibitory activity with IC 50 values ranging as low as 1.0 lM (8,9). In this study, highly predictive atom-based 3D-QSAR models have been generated using PHASE module of Schr€ odinger suite for a set of formylchromane derivatives as PTP 1B inhibitors.…”

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confidence: 99%

Validation of Formylchromane Derivatives as Protein Tyrosine Phosphatase 1B Inhibitors by Pharmacophore Modeling, Atom‐Based 3D‐QSAR and Docking Studies

Malla

Kumar

2013

Chem Biol Drug Des

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Formylchromane derivatives were reported to possess irreversible and selective inhibition on human protein tyrosine phosphatase 1B (PTP 1B). Inhibition of PTP 1B is a molecular level legitimate approach for the management of type 2 diabetes mellitus (T2DM). 3D-QSAR studies were performed on a series of formylchromane derivatives using partial least square (PLS) analysis for correlating molecular architecture of the analogs with their PTP 1B inhibitory activity. A five-point pharmacophore hypothesis with three hydrogen bond acceptors (A) and two aromatic rings (R) as pharmacophoric features was developed using phase module of Schrödinger suite. The hypothesis AAARR.160 was considered as best hypothesis in this study characterized by survival score (3.483), the best cross-validated r² (Q²) (0.774), regression coefficient (0.960), Pearson-R (0.891), and F value (100.3). The results of hypothesis AAARR.160 complimented very closely to interactions witnessed in active site of the ligand-bound complex. The molecular docking simulations into PTP 1B active site also highlighted that biphenyl moiety favorably interacted with amino acid residues lining the lipophilic pocket, and provided hydrophobic interactions with receptor active site. These observations might be useful for further development and optimization of new chemical entities as potential PTP 1B inhibitors prior to its synthesis.

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Formylchromone Derivatives as a Novel Class of Protein Tyrosine Phosphatase 1B Inhibitors.

Abstract: For Abstract see ChemInform Abstract in Full Text.

Cited by 4 publications

References 1 publication

Novel biphenyl compound, VMNS2e, ameliorates streptozotocin‐induced diabetic nephropathy in rats

Novel biphenyl compound, VMNS2e, ameliorates streptozotocin‐induced diabetic nephropathy in rats

Accounting of ligand–receptor interactions to explore and design novel architecture for PTP 1B inhibition: a legitimate approach

Validation of Formylchromane Derivatives as Protein Tyrosine Phosphatase 1B Inhibitors by Pharmacophore Modeling, Atom‐Based 3D‐QSAR and Docking Studies

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