A Novel Phenylchromane Derivative Increases the Rate of Glucose Uptake in L6 Myotubes and Augments Insulin Secretion from Pancreatic Beta-Cells by Activating AMPK

Rozentul, Naomi; Avrahami, Yosef; Shubely, Moran; Levy, Laura M.; Munder, Anna; Cohen, Guy; Cerasi, Erol; Sasson, Shlomo; Gruzman, Arie

doi:10.1007/s11095-017-2271-7

Cited by 10 publications

(3 citation statements)

References 85 publications

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“…As shown in Scheme 1, cyclic diketone 6 was prepared by the reaction of 4,4′‐dihydroxybenzophenone 3 with tosylated 2,2‐dimethyl‐1,3‐propanediol 4 [30] in a stepwise manner. For the latter cyclic reaction, we adopted high dilution conditions (5 mM in DMF) and chose a gem ‐dimethyl substituted linker [31] with the expectation of efficient formation of an intramolecular cyclic compound rather than linear oligomers, and the desired compound 6 , the X‐ray structure of which is shown in Figure S1, was isolated in 33 % yield.…”

Section: Resultsmentioning

confidence: 99%

“…4,4'-Dihydroxybenzophenone 3 (3.31 g, 15.4 mmol), 4 [30] (50.8 g, 123 mmol) and K 2 CO 3 (17.1 g, 124 mmol) were suspended in DMF (200 mL) at 25 °C. The mixture was stirred at 120 °C for 14 h. After ChemPlusChem cooling to 25 °C, the resulting mixture was concentrated in vacuo to remove DMF, and the resulting residue was diluted with water and extracted with CHCl 3 .…”

Section: Preparation Ofmentioning

confidence: 99%

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Bis(triarylmethylium)‐type Macrocyclic Dications: Mechanochromic Emission Extending to the Red Region

et al. 2023

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Macrocyclic dications 22+ composed of two triarylmethylium units were designed and synthesized. In contrast to the reference monocations 1+, macrocyclic dications 22+ exhibited mechanochromic emission extending to the red region (−900 nm), since the luminescence color in a solid state can reversibly change due to their constrained structures granted by alkylene linkers and the choice of a proper counterion. X‐ray diffraction and spectroscopic analyses revealed that such mechanochromic behavior was induced by the crystal‐to‐amorphous transition. A change in the intermolecular interaction of macrocyclic dications 22+ would be the key to realizing a change in the emission pattern, since the color of the molecules did not change by applying mechanical stimuli. These findings may suggest a design strategy for creating a variety of stimuli‐responsive materials, especially for carbocation‐based fluorescent materials.

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Section: Resultsmentioning

confidence: 99%

Section: Preparation Ofmentioning

confidence: 99%

Bis(triarylmethylium)‐type Macrocyclic Dications: Mechanochromic Emission Extending to the Red Region

et al. 2023

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“…The degree of the AMPK activation is usually assessed either by the phosphorylation degree of the main substrates of the kinase [21] or by physiological effects such as decreased lipogenesis, [10] increased glucose uptake, [22] decreased glucose production [23] and others. In the case of AMPKAR, one can most accurately assess the AMPK activity without the need to consider additional pathways of phosphorylation and dephosphorylation of AMPK substrates or complicated mechanisms of integral effects.…”

Section: Resultsmentioning

confidence: 99%

Activating Effect of 3‐Benzylidene Oxindoles on AMPK: From Computer Simulation to High‐Content Screening

et al. 2020

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AMP‐activated protein kinase (AMPK) is currently the subject of intensive study and active discussions. AMPK performs its functions both at the cellular level, providing the switch between energy‐consuming and energy‐producing processes, and at the whole body level, particularly, regulating certain aspects of higher nervous activity and behavior. Control of such a ‘main switch’ compensates dysfunctions and associated diseases. In the present paper, we studied the binding of 3‐benzylidene oxindoles to the kinase domain of the AMPK α‐subunit, which is thought to prevent its interaction with the autoinhibitory domain and thus result in the AMPK activation. For this purpose, we developed the cellular test system based on the AMPKAR plasmid, which implements the FRET effect, synthesized a number of 3‐benzylidene oxindole compounds and simulated their binding to various sites of the kinase domain. The most probable binding site for the studied compounds was established by the correlation of calculated and experimental data. The obtained results allow to analyze various classes of AMPK activators using virtual and high‐content screening.

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Pancreatic β cell models for screening insulin secretagogues and cytotoxicity

Potdar,

Kharat,

Sanap

et al. 2024

J of Applied Toxicology

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In the past 2–3 decades, numerous attempts have been made to create an insulin‐secreting β cell line that maintains normal insulin secretion. However, primary β cell cultures have finite life and, therefore, cannot be used for long‐term experiments. The most widely used insulin‐secreting cell lines are Insulinoma‐1, rat insulinoma cell line, hamster pancreatic β cell line, mouse insulinoma, and β tumor cell line. Insulinoma‐derived cell lines show infinite growth in tissue culture but exhibit varying differences in their insulin responsiveness to glucose levels compared to normal β cells. Despite difficulties with β cell cultures, these cell lines have offered some useful insights in diabetes research concerning physiological functions and pathological investigations. In this review, we describe insulinoma cell lines used for drug screening, insulin secretion, cell viability, proliferation, and other relevant cellular functions. In addition, we have also incorporated recently developed human β cell lines. These cell lines have provided some helpful insights into physiological activities and pathology in diabetes research, despite challenges with β cell culturing. We propose that these cell lines could also be explored for screening Ayurvedic Rasayanas and homeopathy preparations for their cytotoxicity and insulin secretagogue activities to have evidence‐based data on alternative and complementary medicines.

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A Novel Phenylchromane Derivative Increases the Rate of Glucose Uptake in L6 Myotubes and Augments Insulin Secretion from Pancreatic Beta-Cells by Activating AMPK

Abstract: We anticipate that bi-functionality (increased rate of glucose uptake and augmented insulin secretion) will allow the lead compound to be a starting point for the development of a novel class of antidiabetic drugs.

Cited by 10 publications

References 85 publications

Bis(triarylmethylium)‐type Macrocyclic Dications: Mechanochromic Emission Extending to the Red Region

Bis(triarylmethylium)‐type Macrocyclic Dications: Mechanochromic Emission Extending to the Red Region

Activating Effect of 3‐Benzylidene Oxindoles on AMPK: From Computer Simulation to High‐Content Screening

Pancreatic β cell models for screening insulin secretagogues and cytotoxicity

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