Tags

Type your tag names separated by a space and hit enter

PTP1B inhibitors from stems of Angelica keiskei (Ashitaba).
Bioorg Med Chem Lett. 2015; 25(10):2028-32.BM

Abstract

Three new chalcones, xanthoangelols K-M (1-3), together with 19 known compounds were isolated from the stems of Angelica keiskei Koidzumi, a well-known rejuvenated and anti-diabetic plant originated from Japan. The structures of compounds 1-3 were elucidated on the basis of spectroscopic data and Mosher's method. All compounds were evaluated for their inhibitory activity against protein tyrosine phosphatase 1B (PTP1B). Among them, six chalcones, xanthoangelol K (1), xanthoangelol (4), xanthoangelol F (5), 4-hydroxyderricin (6), xanthoangelol D (7), xanthoangelol E (8), and a coumarin, methoxsalen (17), showed strong PTP1B inhibitory effect with IC50 values of 0.82, 1.97, 1.67, 2.47, 3.97, 1.43, and 2.53μg/mL, respectively. A kinetic study revealed that compound 1 inhibited PTP1B with characteristics typical of a competitive inhibitor. Molecular docking simulations elucidated that ring B of 1 may anchor in a pocket of PTP1B and the molecule is stabilized by hydrogen bonds with Arg47, Asp48, and π-π interaction with Phe182 of PTP1B.

Links

Publisher Full Text (DOI)

Authors+Show Affiliations

Li JL
Department of Natural Product Chemistry, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
Gao LX
National Center for Drug Screening, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
Meng FW
Drug Discovery and Design Center, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
Tang CL
National Center for Drug Screening, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
Zhang RJ
Department of Natural Product Chemistry, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
Li JY
National Center for Drug Screening, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
Luo C
Drug Discovery and Design Center, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China. Electronic address: cluo@simm.ac.cn.
Li J
National Center for Drug Screening, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China. Electronic address: jli@simm.ac.cn.
Zhao WM
Department of Natural Product Chemistry, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China. Electronic address: wmzhao@simm.ac.cn.

MeSH

AngelicaChalconesEnzyme InhibitorsHydrogen BondingInhibitory Concentration 50JapanModels, MolecularPlant StemsProtein Tyrosine Phosphatase, Non-Receptor Type 1

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25891102

Citation

Li, Jin-Long, et al. "PTP1B Inhibitors From Stems of Angelica Keiskei (Ashitaba)." Bioorganic & Medicinal Chemistry Letters, vol. 25, no. 10, 2015, pp. 2028-32.
Li JL, Gao LX, Meng FW, et al. PTP1B inhibitors from stems of Angelica keiskei (Ashitaba). Bioorg Med Chem Lett. 2015;25(10):2028-32.
Li, J. L., Gao, L. X., Meng, F. W., Tang, C. L., Zhang, R. J., Li, J. Y., Luo, C., Li, J., & Zhao, W. M. (2015). PTP1B inhibitors from stems of Angelica keiskei (Ashitaba). Bioorganic & Medicinal Chemistry Letters, 25(10), 2028-32. https://doi.org/10.1016/j.bmcl.2015.04.003
Li JL, et al. PTP1B Inhibitors From Stems of Angelica Keiskei (Ashitaba). Bioorg Med Chem Lett. 2015;25(10):2028-32. PubMed PMID: 25891102.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - PTP1B inhibitors from stems of Angelica keiskei (Ashitaba). AU - Li,Jin-Long, AU - Gao,Li-Xin, AU - Meng,Fan-Wang, AU - Tang,Chun-Lan, AU - Zhang,Ru-Jun, AU - Li,Jing-Ya, AU - Luo,Cheng, AU - Li,Jia, AU - Zhao,Wei-Min, Y1 - 2015/04/04/ PY - 2014/12/08/received PY - 2015/04/01/revised PY - 2015/04/03/accepted PY - 2015/4/21/entrez PY - 2015/4/22/pubmed PY - 2016/3/2/medline KW - Angelica keiskei KW - Chalcone KW - Molecular docking KW - PTP1B inhibition SP - 2028 EP - 32 JF - Bioorganic & medicinal chemistry letters JO - Bioorg Med Chem Lett VL - 25 IS - 10 N2 - Three new chalcones, xanthoangelols K-M (1-3), together with 19 known compounds were isolated from the stems of Angelica keiskei Koidzumi, a well-known rejuvenated and anti-diabetic plant originated from Japan. The structures of compounds 1-3 were elucidated on the basis of spectroscopic data and Mosher's method. All compounds were evaluated for their inhibitory activity against protein tyrosine phosphatase 1B (PTP1B). Among them, six chalcones, xanthoangelol K (1), xanthoangelol (4), xanthoangelol F (5), 4-hydroxyderricin (6), xanthoangelol D (7), xanthoangelol E (8), and a coumarin, methoxsalen (17), showed strong PTP1B inhibitory effect with IC50 values of 0.82, 1.97, 1.67, 2.47, 3.97, 1.43, and 2.53μg/mL, respectively. A kinetic study revealed that compound 1 inhibited PTP1B with characteristics typical of a competitive inhibitor. Molecular docking simulations elucidated that ring B of 1 may anchor in a pocket of PTP1B and the molecule is stabilized by hydrogen bonds with Arg47, Asp48, and π-π interaction with Phe182 of PTP1B. SN - 1464-3405 UR - https://www.unboundmedicine.com/medline/citation/25891102/PTP1B_inhibitors_from_stems_of_Angelica_keiskei__Ashitaba__ DB - PRIME DP - Unbound Medicine ER -