11beta-Hydroxysteroid dehydrogenase 1 inhibiting constituents from Eriobotrya japonica revealed by bioactivity-guided isolation and computational approaches

Bioorganic & Medicinal Chemistry
Judith M RollingerAlex Odermatt

Abstract

The inhibition of 11beta-hydroxysteroid dehydrogenase 1 (11beta-HSD1), which catalyzes the conversion of inactive 11-ketoglucocorticoids to active 11beta-hydroxyglucocorticoids, emerged as promising strategy to treat symptoms of the metabolic syndrome, including obesity and type 2 diabetes. In this study the leaves of the anti-diabetic medicinal plant loquat (Eriobotrya japonica) were phytochemically investigated following hints from a pharmacophore-based virtual screening and a bioactivity-guided approach. Determination of the 11beta-HSD1 and 11beta-HSD2 inhibitory activities in cell lysates revealed triterpenes from the ursane type as selective, low micro-molar inhibitors of 11beta-HSD1, that is, corosolic acid (1), 3-epicorosolic acid methyl ester (4), 2-alpha hydroxy-3-oxo urs-12-en-28-oic acid (6), tormentic acid methyl ester (8), and ursolic acid (9). Importantly, a mixture of loquat constituents with moderate activities displayed a pronounced additive effect. By means of molecular modeling studies and the identification of the 11beta-HSD1-inhibiting 11-keto-ursolic acid (17) and 3-acetyl-11-keto-ursolic acid (18) a structure-activity relationship was deduced for this group of pentacyclic triterpenes. The mechanism of act...Continue Reading

References

Jan 1, 1991·Phytochemistry·Y DingT Nohara
Dec 11, 1999·Nucleic Acids Research·H M BermanP E Bourne
Feb 7, 2002·Phytochemistry·Shoko TaniguchiTakashi Yoshida
Feb 13, 2007·Phytomedicine : International Journal of Phytotherapy and Phytopharmacology·J ChenH Q Zhang
Jun 23, 2007·Endocrine, Metabolic & Immune Disorders Drug Targets·Atanas G Atanasov, Alex Odermatt
Mar 28, 2008·Expert Opinion on Investigational Drugs·Katherine A HughesBrian R Walker

❮ Previous
Next ❯

Citations

Oct 20, 2012·Evidence-based Complementary and Alternative Medicine : ECAM·Toshihiro MiuraTorao Ishida
Dec 26, 2015·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Teresa KasererDaniela Schuster
Sep 22, 2012·European Journal of Medicinal Chemistry·René CsukRenate Schäfer
Jan 18, 2011·The Journal of Steroid Biochemistry and Molecular Biology·Denise V KratschmarAlex Odermatt
Jul 28, 2015·Phytochemistry Reviews : Proceedings of the Phytochemical Society of Europe·J Nazaruk, M Borzym-Kluczyk
May 1, 2015·Phytomedicine : International Journal of Phytotherapy and Phytopharmacology·Hui TanKuniyoshi Shimizu
Mar 5, 2013·Phytomedicine : International Journal of Phytotherapy and Phytopharmacology·Juan José Ramírez-EspinosaSamuel Estrada-Soto
Dec 9, 2016·International Journal of Molecular Sciences·Yilong LiuXian Li
Jan 31, 2018·Drug Development Research·Ricardo Guzmán-ÁvilaSamuel Estrada-Soto
Nov 4, 2017·CNS Drugs·Ana B Ramos-HrybAna Lúcia S Rodrigues
Jun 15, 2018·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Catalina MosqueraGuillermo Montoya
Nov 19, 2011·Phytotherapy Research : PTR·Sidney J StohsGilbert R Kaats
Nov 13, 2019·Neurochemical Research·Ana B Ramos-HrybAna Lúcia S Rodrigues
Jul 30, 2020·Molecular Informatics·Ya Chen, Johannes Kirchmair
Mar 7, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Gustavo GutiérrezGuillermo Montoya
Mar 14, 2017·The Journal of Steroid Biochemistry and Molecular Biology·Katharina R BeckAlex Odermatt
Jan 10, 2013·ACS Medicinal Chemistry Letters·Zhao-Kui WanEddine Saiah

❮ Previous
Next ❯

Related Concepts

Related Feeds

CV Disorders & Type 2 Diabetes

This feed focuses on the association of cardiovascular diseases in patients with type 2 diabetes.