title: Novel Imbricatolic acid derivatives as protein tyrosine phosphatase-1B inhibitors: Design, synthesis, biological evaluation and molecular docking.
abstract: Protein tyrosine phosphatase (PTP-1B) antagonizes insulin signaling and is a potential therapeutic target for insulin resistance associated with obesity and type 2 diabetes. To find potential PTP-1B inhibitors, derivatives of Imbricatolic acid (1) have been synthesized by introducing various nitrogenous functionalities at C-15 and C-19 positions. They were evaluated for PTP-1B enzyme inhibition activity. Compounds 3, 6, 14, and 15 exhibited promising PTP-1B inhibitory activity at 10 μM concentrations with IC50 6.3, 6.8, 7.0 and 7.8 values, respectively. Structure activity relationship and molecular docking studies of these derivatives demonstrated that the integrity of the polar substituents were important for significant PTP-1B inhibitory activity. The Imbricatolic acid and active derivatives in this study might represent a starting point for development of new potential PTP-1B inhibitors.
authors.affiliation: Department of Chemistry, University of Lucknow, Lucknow 226007, Uttar Pradesh, India.
authors.forename: Mohammad Faheem
authors.initials: MF
authors.lastname: Khan
authors.affiliation: 'Hygeia', Center of Excellences in Pharmaceutical Sciences (CEPS), Guru Govind Singh Indraprastha University, Sec 16-C, Dwarka, New Delhi 110078, India.
authors.forename: Chandra Sourabh
authors.initials: CS
authors.lastname: Azad
authors.affiliation: Department of Chemistry, University of Lucknow, Lucknow 226007, Uttar Pradesh, India.
authors.forename: Ashok
authors.initials: A
authors.lastname: Kumar
authors.affiliation: Department of Chemistry, University of Lucknow, Lucknow 226007, Uttar Pradesh, India.
authors.forename: Monika
authors.initials: M
authors.lastname: Saini
authors.affiliation: 'Hygeia', Center of Excellences in Pharmaceutical Sciences (CEPS), Guru Govind Singh Indraprastha University, Sec 16-C, Dwarka, New Delhi 110078, India.
authors.forename: Anudeep Kumar
authors.initials: AK
authors.lastname: Narula
authors.affiliation: Department of Chemistry, University of Lucknow, Lucknow 226007, Uttar Pradesh, India. Electronic address: jainsudha2@rediffmail.com.
authors.forename: Sudha
authors.initials: S
authors.lastname: Jain
mesh_terms: D002460:Cell Line; D004224:Diterpenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D004224:Diterpenes; D004791:Enzyme Inhibitors; D011994:Recombinant Proteins; C524691:imbricatolic acid; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1
keywords: Diterpenoids; Imbricatolic acid; PTP-1B-inhibitors; Type 2 diabetes