Novel Imbricatolic acid derivatives as protein tyrosine phosphatase-1B inhibitors: Design, synthesis, biological evaluation and molecular docking.
作者： Mohammad Faheem Khan , Chandra Sourabh Azad , Ashok Kumar , Monika Saini , Anudeep Kumar Narula
DOI: 10.1016/J.BMCL.2016.03.003
关键词:
摘要: Protein tyrosine phosphatase (PTP-1B) antagonizes insulin signaling and is a potential therapeutic target for resistance associated with obesity type 2 diabetes. To find PTP-1B inhibitors, derivatives of Imbricatolic acid (1) have been synthesized by introducing various nitrogenous functionalities at C-15 C-19 positions. They were evaluated enzyme inhibition activity. Compounds 3, 6, 14, 15 exhibited promising inhibitory activity 10 μM concentrations IC50 6.3, 6.8, 7.0 7.8 values, respectively. Structure relationship molecular docking studies these demonstrated that the integrity polar substituents important significant The active in this study might represent starting point development new inhibitors.
sci-hub.se 参考文章(29)
Hsin-Yi Hung, Keduo Qian, Susan L. Morris-Natschke, Chau-Shin Hsu, Kuo-Hsiung Lee, Recent discovery of plant-derived anti-diabetic natural products Natural Product Reports. ,vol. 29, pp. 580- 606 ,(2012) , 10.1039/C2NP00074A
Andrew P. Combs, Recent Advances in the Discovery of Competitive Protein Tyrosine Phosphatase 1B Inhibitors for the Treatment of Diabetes, Obesity, and Cancer Journal of Medicinal Chemistry. ,vol. 53, pp. 2333- 2344 ,(2010) , 10.1021/JM901090B
David J. Newman, Gordon M. Cragg, Natural Products As Sources of New Drugs over the 30 Years from 1981 to 2010 Journal of Natural Products. ,vol. 75, pp. 311- 335 ,(2012) , 10.1021/NP200906S
Christian Wiesmann, Kenneth J Barr, Jenny Kung, Jiang Zhu, Daniel A Erlanson, Wang Shen, Bruce J Fahr, Min Zhong, Lisa Taylor, Mike Randal, Robert S McDowell, Stig K Hansen, Allosteric inhibition of protein tyrosine phosphatase 1B Nature Structural & Molecular Biology. ,vol. 11, pp. 730- 737 ,(2004) , 10.1038/NSMB803
Shu-Chin Yip, Sayanti Saha, Jonathan Chernoff, PTP1B: a double agent in metabolism and oncogenesis Trends in Biochemical Sciences. ,vol. 35, pp. 442- 449 ,(2010) , 10.1016/J.TIBS.2010.03.004
Li-Fan Zeng, Hu-Shan Zhang, Yun-Hua Wang, Tino Sanchez, Yong-Tang Zheng, Nouri Neamati, Ya-Qiu Long, Efficient synthesis and utilization of phenyl-substituted heteroaromatic carboxylic acids as aryl diketo acid isosteres in the design of novel HIV-1 integrase inhibitors Bioorganic & Medicinal Chemistry Letters. ,vol. 18, pp. 4521- 4524 ,(2008) , 10.1016/J.BMCL.2008.07.047
Preeti Rawat, Mohammad F. Khan, Manmeet Kumar, Akhilesh K. Tamarkar, Arvind K. Srivastava, Kamal R. Arya, Rakesh Maurya, Constituents from fruits of Cupressus sempervirens. Fitoterapia. ,vol. 81, pp. 162- 166 ,(2010) , 10.1016/J.FITOTE.2009.08.014
Doina Popov, Novel protein tyrosine phosphatase 1B inhibitors: interaction requirements for improved intracellular efficacy in type 2 diabetes mellitus and obesity control. Biochemical and Biophysical Research Communications. ,vol. 410, pp. 377- 381 ,(2011) , 10.1016/J.BBRC.2011.06.009
Mariano Pertino, Cristina Theoduloz, Marco Bastías, Guillermo Schmeda-Hirschmann, Dimeric Labdane Diterpenes: Synthesis and Antiproliferative Effects Molecules. ,vol. 18, pp. 5936- 5953 ,(2013) , 10.3390/MOLECULES18055936
Cédric Genet, Axelle Strehle, Céline Schmidt, Geoffrey Boudjelal, Annelise Lobstein, Kristina Schoonjans, Michel Souchet, Johan Auwerx, Régis Saladin, Alain Wagner, Structure-activity relationship study of betulinic acid, a novel and selective TGR5 agonist, and its synthetic derivatives: potential impact in diabetes. Journal of Medicinal Chemistry. ,vol. 53, pp. 178- 190 ,(2010) , 10.1021/JM900872Z