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Benzothiazole derivatives upregulate SIRT1 and relevant genes in high-fat fed C57BL/6J mice

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Abstract

SIRT1 is a protein deacetylase and regulates glucose and lipid metabolism through its deacetylase activity for a range of substrates. Growing evidence suggests that activation of SIRT1 can treat diseases such as type II diabetes and cardiovascular diseases. Therefore, novel activators of SIRT1 have aroused enormous interests among scientists. The aim of present study is to synthesize new compounds as SIRT1 activators and to investigate their effects on SIRT1 and relevant genes. The three compounds: (3-benzothiazol-2-yl) aniline (JHJ1), N-(3-(benzothiazol-2-yl)phenyl)-3,4,5-trimethoxybenzamide (JHJ2), and N-(3-(benzothiazol-2-yl)phenyl)-1H-pyrazo-3-carboxamide (JHJ3) were synthesized and their effects on SIRT1 and relevant genes to regulate glucose and lipid metabolism in high-fat diet fed C57BL/6J mice were also addressed. The results showed that relative mRNA expressions of SIRT1, FoxO1, PPARγ, and PGC-1α were significantly up-regulated in the liver, and the glucose, plasma total-cholesterol, hepatic cholesterol, and total triglyceride concentration were markedly lowered by JHJ1, JHJ2, and JHJ3 supplementation, respectively. These results suggest that benzothiazole derivatives HJ1, JHJ2, and JHJ3 supplementation could modulate the plasma lipids metabolism and blood glucose-lowering action in high-fat fed mice through regulation of SIRT1 and relevant genes.

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Abbreviations

SIRT1:

Silent information regulator 1

FoxO1:

Forkhead box O1

PPARγ:

Peroxisome proliferators activated receptor γ

PGC-1α:

Peroxisome proliferator-activated receptor gamma coactivator 1-alpha

HDL-C:

High-density lipoprotein cholesterol

total-C:

Total-cholesterol

TG:

Triglycerides

PPA:

Polyphosphoric acid

EDCI:

N-(3-Dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride

Et3N:

Triethylamine

DMAP:

4-Dimethylamiopryidine

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Acknowledgments

This work was supported by Grants from the National Natural Science Foundation of China (Grant no. 81072521) and Tianjin University of Science & Technology (Grant No. 20100411).

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Authors and Affiliations

  1. Key Laboratory of Industrial Microbiology, Ministry of Education, College of Biotechnology, Tianjin University of Science & Technology, 13th Avenue, Tianjin Economic and Technological Development Area (TEDA), Tianjin, 300457, China

    Shaolong Jia, Weizhu Liu, Peng Yu & Erbing Hua

  2. Tianjin Centers for Disease Control & Prevention, No. 6 Huayue Road, Hedong District, Tianjin, 300011, China

    Qing Gu, Penghui Zhou, Xu Su & Jingshu Zhang

  3. Shanxi Medical University Clinical Training Centre, Taiyuan, 030001, Shanxi, China

    Xiaoling Xu

  4. Laboratory and Equipment Management Office, Tianjin University of Science & Technology, 13th Avenue, Tianjin Economic and Technological Development Area (TEDA), Tianjin, 300457, China

    Weichun Fang

  5. Key Laboratory of Food Nutrition and Safety, Tianjin University of Science & Technology, 13th Avenue, Tianjin Economic and Technological Development Area (TEDA), Tianjin, 300457, China

    Hao Wang

Authors
  1. Qing Gu
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  2. Penghui Zhou
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  3. Xiaoling Xu
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  4. Weichun Fang
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  5. Shaolong Jia
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  7. Xu Su
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  8. Jingshu Zhang
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  9. Hao Wang
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  10. Peng Yu
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  11. Erbing Hua
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Correspondence to Erbing Hua.

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Gu, Q., Zhou, P., Xu, X. et al. Benzothiazole derivatives upregulate SIRT1 and relevant genes in high-fat fed C57BL/6J mice. Med Chem Res 24, 2454–2460 (2015). https://doi.org/10.1007/s00044-014-1307-3

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  • DOI: https://doi.org/10.1007/s00044-014-1307-3

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