title: Protein tyrosine phosphatase 1B inhibitors isolated from Artemisia roxburghiana.
abstract: Artemisia roxburghiana is used in traditional medicine for treating various diseases including diabetes. The present study was designed to evaluate the antidiabetic potential of active constituents by using protein tyrosine phosphatase 1B (PTP1B) as a validated target for management of diabetes. Various compounds were isolated as active principles from the crude methanolic extract of aerial parts of A. roxburghiana. All compounds were screened for PTP1B inhibitory activity. Molecular docking simulations were performed to investigate the mechanism behind PTP1B inhibition of the isolated compound and positive control, ursolic acid. Betulinic acid, betulin and taraxeryl acetate were the active PTP1B principles with IC50 values 3.49 ± 0.02, 4.17 ± 0.03 and 87.52 ± 0.03 µM, respectively. Molecular docking studies showed significant molecular interactions of the triterpene inhibitors with Gly220, Cys215, Gly218 and Asp48 inside the active site of PTP1B. The antidiabetic activity of A. roxburghiana could be attributed due to PTP1B inhibition by its triterpene constituents, betulin, betulinic acid and taraxeryl acetate. Computational insights of this study revealed that the C-3 and C-17 positions of the compounds needs extensive optimization for the development of new lead compounds.
authors.affiliation: a H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi , Karachi , Pakistan .
authors.forename: Muhammad Raza
authors.initials: MR
authors.lastname: Shah
authors.affiliation: b Department of Chemistry , Hazara University , Mansehra , Pakistan .
authors.lastname: Ishtiaq
authors.affiliation: c Department of Pharmacy , University of Peshawar , Peshawar , Pakistan .
authors.forename: Syed Muhammad
authors.initials: SM
authors.lastname: Hizbullah
authors.affiliation: d Pharmacognosy Research Laboratories, Medway School of Science, University of Greenwich , Kent , UK .
authors.forename: Solomon
authors.initials: S
authors.lastname: Habtemariam
authors.affiliation: e Department of Chemical Sciences , University of Naples "Federico II" , Naples , Italy .
authors.forename: Armando
authors.initials: A
authors.lastname: Zarrelli
authors.affiliation: f Department of Chemistry , University of Karachi , Karachi , Pakistan , and.
authors.forename: Akhtar
authors.initials: A
authors.lastname: Muhammad
authors.affiliation: g Department of Pharmacy , University of Pavia , Pavia , Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Collina
authors.affiliation: c Department of Pharmacy , University of Peshawar , Peshawar , Pakistan .
authors.forename: Inamulllah
authors.initials: I
authors.lastname: Khan
mesh_terms: D019306:Artemisia / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D006801:Humans; D007004:Hypoglycemic Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D035261:Plant Components, Aerial / Q000737:chemistry; D018515:Plant Leaves / Q000737:chemistry; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D004791:Enzyme Inhibitors; D007004:Hypoglycemic Agents; C516607:PTPN1 protein, human; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1
keywords: Artemisia roxburghiana; PTP1B; docking; triterpenes; ursolic acid