Design, synthesis and biological evaluation of novel arylidine-malononitrile derivatives as non-carboxylic inhibitors of protein tyrosine phosphatase 1B

详细信息    查看全文

• 作者：Girdhar Singh Deora (1) (2)
  Chandrabose Karthikeyan (1)
  N. S. Hari Narayana Moorthy (1) (3)
  Vandana Rathore (2) (4)
  Arun K. Rawat (5)
  Akhilesh K. Tamrakar (5)
  A. K. Srivastava (5)
  Piyush Trivedi (1)
  
• 关键词：PTP1B ; Diabetes ; Arylidine malononitrile ; Oxadiazole ; Non ; carboxylic acid inhibitors ; Docking study
• 刊名：Medicinal Chemistry Research
• 出版年：2013
• 出版时间：November 2013
• 年：2013
• 卷：22
• 期：11
• 页码：5344-5348
• 全文大小：
• 作者单位：Girdhar Singh Deora (1) (2)
  Chandrabose Karthikeyan (1)
  N. S. Hari Narayana Moorthy (1) (3)
  Vandana Rathore (2) (4)
  Arun K. Rawat (5)
  Akhilesh K. Tamrakar (5)
  A. K. Srivastava (5)
  Piyush Trivedi (1)
  
  1. School of Pharmaceutical Sciences, Rajiv Gandhi Proudyogiki Vishwavidyalaya, Airport Bypass Road, Gandhi Nagar, Bhopal, 462036, MP, India
  2. Dr. Reddy’s Institute of Life Sciences, University of Hyderabad Campus, Gachibowli, Hyderabad, 500046, India
  3. Department of Chemistry and Biochemistry, Faculty of Sciences, University of Porto, 687, Rua de Campo Alegre, 4169-007, Porto, Portugal
  4. B. N. Institute of Pharmaceutical Sciences, Udaipur, 313001, Rajasthan, India
  5. Division of Biochemistry, Central Drug Research Institute, Lucknow, 226001, UP, India
  
• ISSN：1554-8120

文摘

In this study, we describe the design, synthesis, biological evaluation and molecular modelling studies of novel non-carboxylic arylidine malononitrile-based molecules as Protein Tyrosine Phosphatase 1B (PTP1B) inhibitors. The synthesized derivatives were evaluated in vitro for glucose reuptake using L6 muscle cell lines and enzymatic assay against PTP1B. The biological activity results showed that the 2-methoxy substituted (14b) compound exhibited significant activity in both the assays. The unsubstituted compound (14a) also possessed comparable activity on glucose reuptake in L6 muscle cell lines and better inhibitory activity on PTP1B enzyme assays. Docking analysis was performed on the most potent compound of the series to understand the nature of interactions governing the binding of the designed molecule with the PTP1B enzyme.