2-(3-Benzoylthioureido)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylic acid ameliorates metabolic disorders in high-fat diet-fed mice

Zhang, Jin; Zhang, Lina; Chen, Dongmei; Fu, Yangyang; Zhang, Feng; Yang, Lingling; Xia, Chunmei; Jiang, Haowen; Tang, Chunlan; Xie, Zhifu; Yang, Fan; Li, Jia; Tang, Jie

doi:10.1038/aps.2014.149

Cited by 6 publications

(3 citation statements)

References 57 publications

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“…AMPK regulates SREBP1 activity and inhibits lipogenesis in part via the inhibition of mTOR in the fatty liver (19,35). mTOR signaling has been shown to regulate lipid metabolic processes, including DNL and triglyceride synthesis (36,37).…”

Section: Discussionmentioning

confidence: 99%

Tangshen formula attenuates hepatic steatosis by inhibiting hepatic lipogenesis and augmenting fatty acid oxidation in db/db mice

Kong

Zhang

Zhao

et al. 2016

International Journal of Molecular Medicine

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Tangshen formula (TSF), a well-prescribed traditional Chinese formula, has been used in the treatment of diabetic nephropathy. However, whether TSF ameliorates dyslipidemia and liver injury associated with diabetes remains unclear. In this study, we examined the effects of TSF on lipid profiles and hepatic steatosis in db/db mice. For this purpose, 8-week-old db/db mice were treated with TSF or saline for 12 weeks via gavage and db/m mice were used as controls. Body weight and blood glucose levels were monitored weekly and bi-weekly, respectively. Blood samples were obtained for the analysis of lipids and enzymes related to hepatic function, and liver tissues were analyzed by histology, immunohistochemistry and molecular examination. The results revealed that TSF markedly reduced body weight, liver index [liver/body weight (LW/BW)] and improved lipid profiles, hepatic function and steatosis in db/db mice. TSF induced the phosphoralation of AMP-activated protein kinase and inhibited the activity of sterol regulatory element-binding protein 1 together with the inhibition of the expression of genes involved in de novo lipogenesis (DNL) and gluconeogenesis, such as fatty acid synthase (FAS), acetyl-CoA carboxylase (ACC), stearoyl CoA desaturase 1 (SCD1), glucose-6-phosphatase (G6pc) and phosphoenolpyruvate carboxykinase 1 (Pck1). Additionally, the silent mating type information regulation 2 homolog 1 (Sirt1)/peroxisome proliferator-activated receptor α (PPARα)/malonyl-CoA decarboxylase (MLYCD) cascade was potently activated by TSF in the liver and skeletal muscle of db/db mice, which led to enhanced fatty acid oxidation. These findings demonstrated that TSF attenuated hepatic fat accumulation and steatosis in db/db mice by inhibiting lipogenesis and augmenting fatty acid oxidation.

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Section: Discussionmentioning

confidence: 99%

Tangshen formula attenuates hepatic steatosis by inhibiting hepatic lipogenesis and augmenting fatty acid oxidation in db/db mice

Kong

Zhang

Zhao

et al. 2016

International Journal of Molecular Medicine

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“…In addition, the model appears to display a pro-inflammatory and pro-fibrotic state that is associated with the human metabolic syndrome [ 25 , 26 ]. The model has been published extensively in the evaluation of anti-diabetic and anti-obesity agents [ 27 – 31 ].…”

Section: Introductionmentioning

confidence: 99%

Glucose dysregulation and response to common anti-diabetic agents in the FATZO/Pco mouse

Peterson¹,

Jackson²,

Zimmerman³

et al. 2017

PLoS ONE

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The FATZO/Pco mouse is the result of a cross of the C57BL/6J and AKR/J strains. The crossing of these two strains and the selective inbreeding for obesity, insulin resistance and hyperglycemia has resulted in an inbred strain exhibiting obesity in the presumed presence of an intact leptin pathway. Routinely used rodent models for obesity and diabetes research have a monogenic defect in leptin signaling that initiates obesity. Given that obesity and its sequelae in humans are polygenic in nature and not associated with leptin signaling defects, the FATZO mouse may represent a more translatable rodent model for study of obesity and its associated metabolic disturbances. The FATZO mouse develops obesity spontaneously when fed a normal chow diet. Glucose intolerance with increased insulin levels are apparent in FATZO mice as young as 6 weeks of age. These progress to hyperglycemia/pre-diabetes and frank diabetes with decreasing insulin levels as they age. The disease in these mice is multi-faceted, similar to the metabolic syndrome apparent in obese individuals, and thus provides a long pre-diabetic state for determining the preventive value of new interventions. We have assessed the utility of this new model for the pre-clinical screening of agents to stop or slow progression of the metabolic syndrome to severe diabetes. Our assessment included: 1) characterization of the spontaneous development of disease, 2) comparison of metabolic disturbances of FATZO mice to control mice and 3) validation of the model with regard to the effectiveness of current and emerging anti-diabetic agents; rosiglitazone, metformin and semaglutide. Conclusion: Male FATZO mice spontaneously develop significant metabolic disease when compared to normal controls while maintaining hyperglycemia in the presence of high leptin levels and hyperinsulinemia. The disease condition responds to commonly used antidiabetic agents.

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“…Heterocyclic compounds include several carbon atoms that have been imposed in a ring (carbocyclic compounds), and also some carbon atoms have been replaced by nitrogen or oxygen and or sulfur as a hetero atom 1 – 4 . As is well-known, the five-membered heteroaromatic rings containing oxygen and sulfur atoms, furan and thiophene, are frequently used as building blocks in many drugs 5 – 7 . Aminoquinoline derivatives that are based on thiophene and furan rings have been found to be potent inhibitors of polymerization of b-hematin and also is antimalarials 8 .…”

Section: Introductionmentioning

confidence: 99%

A computer-aided method for controlling chemical resistance of drugs using RRKM theory in the liquid phase

Douroudgari

Vahedpour

2021

Sci Rep

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The chemical resistance of drugs against any change in their composition and studying the rate of multiwell-multichannel reactions in the liquid phase, respectively, are the important challenges of pharmacology and chemistry. In this article, we investigate two challenges together through studying drug stability against its unimolecular reactions in the liquid phase. Accordingly, multiwell-multichannel reactions based on 1,4-H shifts are designed for simplified drugs such as 3-hydroxyl-1H-pyrrol-2(5H)-one, 3-hydroxyfuran-2(5H)-one, and 3-hydroxythiophen-2(5H)-one. After that, the reverse and forward rate constants are calculated by using the Rice Ramsperger Kassel Marcus theory (RRKM) and Eckart tunneling correction over the 298–360 K temperature range. Eventually, using the obtained rate constants, we can judge drug resistance versus structural changes. To attain the goals, the potential energy surfaces of all reactions are computed by the complete basis set-quadratic Becke3 composite method, CBS-QB3, and the high-performance meta hybrid density functional method, M06-2X, along with the universal Solvation Model based on solute electron Density, SMD, due to providing more precise and efficient results for the barrier heights and thermodynamic studies. To find the main reaction pathway of the intramolecular 1,4-H shifts in the target molecules, all possible reaction pathways are considered mechanistically in the liquid phase. Also, the direct dynamics calculations that carry out by RRKM theory on the modeled pathways are used to distinguish the main reaction pathway. As the main finding of this research, the results of quantum chemical calculations accompanied by the RRKM/Eckart rate constants are used to predict the stability of drugs. This study proposes a new way to examine drug stability by the computer-aided reaction design of target drugs. Our results show that 3-hydroxyfuran-2(5H)-one based drugs are the most stable and 3-hydroxythiophen-2(5H)-one based drugs are more stable than 3-hydroxy-1H-pyrrol-2 (5H)-one based drugs in water solution.

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2-(3-Benzoylthioureido)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylic acid ameliorates metabolic disorders in high-fat diet-fed mice

Cited by 6 publications

References 57 publications

Tangshen formula attenuates hepatic steatosis by inhibiting hepatic lipogenesis and augmenting fatty acid oxidation in db/db mice

Tangshen formula attenuates hepatic steatosis by inhibiting hepatic lipogenesis and augmenting fatty acid oxidation in db/db mice

Glucose dysregulation and response to common anti-diabetic agents in the FATZO/Pco mouse

A computer-aided method for controlling chemical resistance of drugs using RRKM theory in the liquid phase

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