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Nagat Ghareb, Norhan M El-Sayed, Reda Abdelhameed, Koji Yamada, Mohamed Saleh Elgawish
Targeting of protein tyrosine phosphatase-1B (PTP1B) has emerged as a promising strategy for therapeutic intervention of diabetes and obesity. Investigation of new inhibitors with good bioavailability and high selectivity is the major challenge of drug discovery program targeting PTP1B. Therefore, herein, new neutral benzene-sulfonamide containing compounds were designed, synthesized and biologically evaluated as potent PTP1B inhibitors. New series of thiazolidine, oxazolidine, thiazinan, oxazinan, oxazole, thiazole, tetrazole, cyanopyridine, chromenone, and iminochromene of benzene-sulfonamide derivatives (MSE-1 to MSE-15) were synthesized in a good yield under mild condition using sulfadiazine as a starting material...
January 31, 2019: Bioorganic Chemistry
Eleni Kyriakou, Stefanie Schmidt, Garron T Dodd, Katrin Pfuhlmann, Stephanie E Simonds, Dominik Lenhart, Arie Geerlof, Sonja C Schriever, Meri De Angelis, Karl-Werner Schramm, Oliver Plettenburg, Michael A Cowley, Tony Tiganis, Matthias H Tschöp, Paul T Pfluger, Michael Sattler, Ana C Messias
Celastrol is a natural pentacyclic triterpene used in traditional Chinese medicine with significant weight-lowering effects. Celastrol-administered mice at 100 μg/kg decrease food consumption and body weight via a leptin-dependent mechanism, yet its molecular targets in this pathway remain elusive. Here, we demonstrate in vivo that celastrol-induced weight loss is largely mediated by the inhibition of leptin negative regulators protein tyrosine phosphatase (PTP) 1B (PTP1B) and T-cell PTP (TCPTP) in the arcuate nucleus (ARC) of the hypothalamus...
December 7, 2018: Journal of Medicinal Chemistry
Ashima Singh, Harjinder Singh, J M Khurana
We have reported synthesis of a novel 1,2,3-triazole conjugate of lithocholic acid by 1,3-dipolar cycloaddition reaction. The molecular properties such as geometry, conformations, bond lengths and dihedral angles were investigated theoretically. The bond order analysis was performed using Wiberg bond order (WBO), Fuzzy bond order (FBO) and Laplacian bond order (MBO) method. Electronic properties of molecule such as electrostatic surface potential analysis, frontier molecular orbital analysis, reduced density gradient, total density of states, and global chemical reactivity indices have been investigated...
November 22, 2018: Computational Biology and Chemistry
Sergio Hidalgo-Figueroa, Samuel Estrada-Soto, Juan José Ramírez-Espinosa, Paolo Paoli, Giulia Lori, Ismael León-Rivera, Gabriel Navarrete-Vázquez
This work presents the synthesis of two hybrid compounds (1 and 2) with thiazolidine-2,4-dione structure as a central scaffold which were further screened in combo (in vitro as PTP-1B inhibitors, in vivo antihyperglycemic activity, in silico toxicological profile and molecular docking). Compound 1 was tested in the enzymatic assay showing an IC50 = 9.6 ± 0.5 μM and compound 2 showed about a 50% of inhibition of PTP-1B at 20 μM. Therefore, compound 1 was chosen to test its antihyperglycemic effect in a rat model for non-insulin-dependent diabetes mellitus (NIDDM), which was determined at 50 mg/kg in a single dose...
November 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Miguel Ángel Herrera-Rueda, Hugo Tlahuext, Paolo Paoli, Abraham Giacoman-Martínez, Julio César Almanza-Pérez, Horacio Pérez-Sánchez, Abraham Gutiérrez-Hernández, Fabiola Chávez-Silva, Elix Alberto Dominguez-Mendoza, Samuel Estrada-Soto, Gabriel Navarrete-Vazquez
In this study, we synthesized five N-Boc-L-tyrosine-based analogues to glitazars. The in vitro effects of compounds 1-5 on protein tyrosine phosphatase 1B (PTP-1B), peroxisome proliferator-activated receptor alpha and gamma (PPARα/γ), glucose transporter type-4 (GLUT-4) and fatty acid transport protein-1 (FATP-1) activation are reported in this paper. Compounds 1 and 3 were the most active in the in vitro PTP-1B inhibition assay, showing IC50 s of approximately 44 μM. Treatment of adipocytes with compound 1 increased the mRNA expression of PPARγ and GLUT-4 by 8- and 3-fold, respectively...
December 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Lorenzo Cecchi, Marzia Innocenti, Silvia Urciuoli, Marco Arlorio, Paolo Paoli, Nadia Mulinacci
This paper investigates the phenolic composition of 17 monocultivar commercial cold-pressed grape seed oils. Chromatographic profiles showed the presence of more than 28 molecules, 11 of which were successfully identified by HPLC-DAD-MS-TOF and HPLC-FLD analysis. Pinoresinol, ethyl caffeate and ethyl gallate were detected for the first time in these oils. The total phenolic content ranged between 0.83 mg/kg for Viognier sample to 15.16 mg/kg for Merlot org sample. The detected ethyl esters can be suggested as markers to evaluate the intensity of fermentation in grape seeds before oil extraction, and to control the sensorial quality of the produced oils...
January 15, 2019: Food Chemistry
Salamet Edirs, Lan Jiang, XueLei Xin, Haji Akber Aisa
Kursi Wufarikun Ziyabit (KWZ) is a traditional prescription that used in folk tea drinking for its health care effect in treatment of type 2 diabetes mellitus (T2DM) in central Asia. However, the underlying mechanism of KWZ in T2DM has not been investigated extensively. This study designed to observe the effect of KWZ on glucose consumption and assess the molecular mechanism on associated proteins in insulin signaling and ER stress pathway in L6 rat skeletal muscle cells. The results showed that, KWZ exhibited proteins of PTP-1B and α-glycosidase inhibitory activity in vitro...
June 2018: Journal of Pharmacological Sciences
Mohammad Faheem Khan, Arun Kumar Rawat, Shahnaaz Khatoon, Mohd Kamil Hussain, Arvind Mishra, Devendra Singh Negi
Background: To investigate the antidiabetic effect of Himalayan Medicinal plants from India viz . Melia azedarach (Family: Meliaceae), Zanthoxylum alatum (Family: Rutaceae), Tanacetum nubigenum (Family: Asteraceae) using in-vitro as well as in-vivo approaches. Methods: Their effects were examined on stimulation of glucose uptake by C2C12 cultured cell line, inhibitory effect on human recombinant Protein tyrosine phosphatase-1B (PTP-1B) and followed by the hypoglycaemic activity of extracts in Streptozotocin (STZ) induced diabetic rats...
June 2018: Integrative Medicine Research
Maciej Wójcik, Agata Krawczyńska, Hanna Antushevich, Andrzej Przemysław Herman
The growth hormone (GH) plays a key role in the regulation of metabolic processes in an organism. Determination of the correct structure and functioning of the growth hormone receptor (GHR) allowed for a more detailed research of its post-receptor regulators, which substantially influences its signal transduction. This review is focused on the description of the post-receptor inhibitors of the GHR-JAK2-STAT pathway, which is one of the most important pathways in the transduction of the somatotropic axis signal...
June 22, 2018: International Journal of Molecular Sciences
Delfly Booby Abdjul, Hiroyuki Yamazaki, Syu-Ichi Kanno, Ryota Kirikoshi, Ayako Tomizawa, Ohgi Takahashi, Wilmar Maarisit, Fitje Losung, Henki Rotinsulu, Defny Silvia Wewengkang, Deiske Adeliene Sumilat, Magie Melanie Kapojos, Michio Namikoshi
Two sesquiterpene lactones with the (9R)-eudesman-9,12-olide framework, wedelolides I and J, have been isolated together with five eudesmanolide sesquiterpenes and twelve ent-kaurene diterpenes from the aerial parts of Indonesian Wedelia prostrata. The absolute configurations of wedelolides I and J, proposed in the previous communication, were proven by comparing their experimental Electronic Circular Dichroism (ECD) spectra with the calculated ECD spectrum of wedelolide I. The phytochemical study on the aerial parts of Okinawan Wedelia chinensis led to the isolation of three other eudesmanolide sesquiterpenes in addition to the three sesquiterpenes and eleven diterpenes isolated from the Indonesian W...
2018: Chemical & Pharmaceutical Bulletin
Selvaraj Kunjiappan, Theivendren Panneerselvam, Parvathy Prasad, Sunija Sukumaran, Balasubramanian Somasundaram, Murugesan Sankaranarayanan, Indhumathy Murugan, Pavadai Parasuraman
The aim of the present study is to develop keratin nanoparticles (NPs) encapsulated in Dunaliella bardawil (D. bardawil) biomass, in order to improve their glucose uptake in 3T3-L1 adipocytes. The graph theoretical approach has provided a platform to identify PTP-1B and AMPK as an effective drug target. Docking results of the active constituents of D. bardawil showed a strong interaction with binding pockets of identified PTP-1B and AMPK. The encapsulation efficiency, drug release, stability and physicochemical properties of prepared NPs were analyzed using UV-visible spectrophotometry, Fourier transform infrared spectrophotometry, x-ray diffraction, scanning and tunneling electron microscopy, and Zeta size analysis...
May 4, 2018: Biomedical Materials
Ashish D Patel, Rahul Barot, Inaxi Parmar, Ishan Panchal, Umang Shah, Mehul Patel, Bharat Mishtry
1,6-Dihydropyrimidine exerts notable pharmacological efficiency and emerged as integral backbones for treatment of type-II diabetes mellitus. To optimize the in vitro and in-silico study we carried out on substituted 1,6-Dihydropyrimidine. The objective of the present study is to evaluate the binding interaction of 1,6-Dihydropyrimidine compounds with protein tyrosine phosphatase (PTP1B) enzyme and also check ADME/T properties of best scored compounds. The in-silico study (docking) was carried out through target protein tyrosine phosphatase (PTP1B) retrieved from protein data bank having PDB ID: 2QBS and the anti diabetic activity of the test compounds was tested against protein tyrosine phosphatase (PTP1B) enzyme by using Calbiochem® PTP1B colorimetric assay kit...
April 26, 2018: Current Computer-aided Drug Design
Hiroyuki Yamazaki, Kenta Takahashi, Natsuki Iwakura, Tatsuki Abe, Masanari Akaishi, Satomi Chiba, Michio Namikoshi, Ryuji Uchida
A new polyenyl-α-pyrone polyketide, aspopyrone A (1), was isolated from a culture broth of Okinawan plant-associated Aspergillus sp. TMPU1623 by solvent extraction, ODS column chromatography, and preparative HPLC (ODS). The structure of 1 was assigned based on NMR experiments. Compound 1 exhibited protein tyrosine phosphatase (PTP) 1B and T-cell PTP (TCPTP) inhibitory activities with IC50 values of 6.7 and 6.0 μM, respectively.
August 2018: Journal of Antibiotics
Henki Rotinsulu, Hiroyuki Yamazaki, Shino Sugai, Natsuki Iwakura, Defny S Wewengkang, Deiske A Sumilat, Michio Namikoshi
Cladosporamide A (1), a new protein tyrosine phosphatase (PTP) 1B inhibitor, was isolated together with a known prenylated flavanone derivative (2) from the culture broth of an Indonesian marine sponge-derived Cladosporium sp. TPU1507 by solvent extraction, ODS column chromatography, and preparative HPLC (ODS). The structure of 1 was elucidated based on 1D and 2D NMR data. Compound 1 modestly inhibited PTP1B and T-cell PTP (TCPTP) activities with IC50 values of 48 and 54 μM, respectively. The inhibitory activity of 2 against PTP1B (IC50  = 11 μM) was approximately 2-fold stronger than that against TCPTP (IC50  = 27 μM)...
June 2018: Journal of Natural Medicines
Gabriel Keine Kuga, Vitor Rosetto Muñoz, Rafael Calais Gaspar, Susana Castelo Branco Ramos Nakandakari, Adelino Sanchez Ramos da Silva, José Diego Botezelli, José Alexandre Curiacos de Almeida Leme, Ricardo José Gomes, Leandro Pereira de Moura, Dennys Esper Cintra, Eduardo Rochete Ropelle, José Rodrigo Pauli
The insulin and Brain-Derived Neurotrophic Factor (BDNF) signaling in the hippocampus promotes synaptic plasticity and memory formation. On the other hand, aging is related to the cognitive decline and is the main risk factor for Alzheimer's Disease (AD). The Protein-Tyrosine Phosphatase 1B (PTP1B) is related to several deleterious processes in neurons and emerges as a promising target for new therapies. In this context, our study aims to investigate the age-related changes in PTP1B content, insulin signaling, β-amyloid content, and Tau phosphorylation in the hippocampus of middle-aged rats...
April 2018: Experimental Gerontology
Ricardo Guzmán-Ávila, Virginia Flores-Morales, Paolo Paoli, Guido Camici, Juan José Ramírez-Espinosa, Litzia Cerón-Romero, Gabriel Navarrete-Vázquez, Sergio Hidalgo-Figueroa, Maria Yolanda Rios, Rafael Villalobos-Molina, Samuel Estrada-Soto
Hit, Lead & Candidate Discovery Protein tyrosine phosphatase 1B (PTP-1B) has attracted interest as a novel target for the treatment of type 2 diabetes, this because its role in the insulin-signaling pathway as a negative regulator. Thus, the aim of current work was to obtain seven ursolic acid derivatives as potential antidiabetic agents with PTP-1B inhibition as main mechanism of action. Furthermore, derivatives 1-7 were submitted in vitro to enzymatic PTP-1B inhibition being 3, 5, and 7 the most active compounds (IC50  = 5...
March 2018: Drug Development Research
Delfly B Abdjul, Hiroyuki Yamazaki, Wilmar Maarisit, Henki Rotinsulu, Defny S Wewengkang, Deiske A Sumilat, Magie M Kapojos, Fitje Losung, Kazuyo Ukai, Michio Namikoshi
During the search for new protein tyrosine phosphatase (PTP) 1B inhibitors, EtOH extracts from the aerial parts of Lantana camara L. (lantana) collected at Manado (Indonesia) and two subtropical islands in Japan (Ishigaki and Iriomote Islands, Okinawa) exhibited potent inhibitory activities against PTP1B in an enzyme assay. Four previously undescribed oleanane triterpenes were isolated together with known triterpenes and flavones from the Indonesian lantana. The EtOH extracts of lantana collected in Ishigaki and Iriomote Islands exhibited different phytochemical profiles from each other and the Indonesian lantana...
December 2017: Phytochemistry
David Gozal, Abdelnaby Khalyfa, Zhuanghong Qiao, Mahzad Akbarpour, Rosanna Maccari, Rosaria Ottanà
Study Objectives: Sleep fragmentation (SF) is highly prevalent and has emerged as an important contributing factor to obesity and metabolic syndrome. We hypothesized that SF-induced increases in protein tyrosine phosphatase-1B (PTP-1B) expression and activity underlie increased food intake, inflammation, and leptin and insulin resistance. Methods: Wild-type (WT) and ObR-PTP-1b-/- mice (Tg) were exposed to SF and control sleep (SC), and food intake was monitored...
September 1, 2017: Sleep
Dimitrios Angelis, Maria Delivoria-Papadopoulos
BACKGROUND: Protein tyrosine phosphatases (PTPs) in conjunction with protein tyrosine kinases (PTKs) regulate cellular processes by posttranslational modifications of signal transduction proteins. PTP nonreceptor type 1B (PTP-1B) is an enzyme of the PTP family. We have previously shown that hypoxia induces an increase in activation of a class of nonreceptor PTK, the Src kinases. In the present study, we investigated the changes that occur in the expression of PTP-1B in the cytosolic component of the brain of newborn piglets acutely after hypoxia as well as long term for up to 2 weeks...
2017: Mediators of Inflammation
Sodik Numonov, Salamet Edirs, Khayrulla Bobakulov, Muhammad Nasimullah Qureshi, Khurshed Bozorov, Farukh Sharopov, William N Setzer, Haiqing Zhao, Maidina Habasi, Mizhgona Sharofova, Haji Akber Aisa
The root of Geranium collinum Steph is known in Tajik traditional medicine for its hepatoprotective, antioxidant, and anti-inflammatory therapeutic effects. The present study was conducted to evaluate of potential antidiabetic, antioxidant activities, total polyphenolic and flavonoid content from the different extracts (aqueous, aqueous-ethanolic) and individual compounds isolated of the root parts of G. collinum . The 50% aqueous-ethanolic extract possesses potent antidiabetic activity, with IC50 values of 0...
June 13, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
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