Potent inhibition of human phosphodiesterase-5 by icariin derivatives - PubMed (original) (raw)
doi: 10.1021/np800049y. Epub 2008 Sep 9.
Affiliations
- PMID: 18778098
- DOI: 10.1021/np800049y
Potent inhibition of human phosphodiesterase-5 by icariin derivatives
Mario Dell'Agli et al. J Nat Prod. 2008 Sep.
Abstract
Plant extracts traditionally used for male impotence (Tribulus terrestris, Ferula hermonis, Epimedium brevicornum, Cinnamomum cassia), and the individual compounds cinnamaldehyde, ferutinin, and icariin, were screened against phosphodiesterase-5A1 (PDE5A1) activity. Human recombinant PDE5A1 was used as the enzyme source. Only E. brevicornum extract (80% inhibition at 50 microg/mL) and its active principle icariin (1) (IC50 5.9 microM) were active. To improve its inhibitory activity, 1 was subjected to various structural modifications. Thus, 3,7-bis(2-hydroxyethyl)icaritin (5), where both sugars in 1 were replaced with hydroxyethyl residues, potently inhibited PDE5A1 with an IC50 very close to that of sildenafil (IC50 75 vs 74 nM). Thus, 5 was 80 times more potent than 1, and its selectivity versus phosphodiesterase-6 (PDE6) and cyclic adenosine monophosphate-phosphodiesterase (cAMP-PDE) was much higher in comparison with sildenafil. The improved pharmacodynamic profile and lack of cytotoxicity on human fibroblasts make compound 5 a promising candidate for further development.
Similar articles
- Highly potent and selective chiral inhibitors of PDE5: an illustration of Pfeiffer's rule.
Bunnage ME, Mathias JP, Wood A, Miller D, Street SD. Bunnage ME, et al. Bioorg Med Chem Lett. 2008 Dec 1;18(23):6033-6. doi: 10.1016/j.bmcl.2008.10.037. Epub 2008 Oct 11. Bioorg Med Chem Lett. 2008. PMID: 18951784 - The discovery of novel, potent and selective PDE5 inhibitors.
Bi Y, Stoy P, Adam L, He B, Krupinski J, Normandin D, Pongrac R, Seliger L, Watson A, Macor JE. Bi Y, et al. Bioorg Med Chem Lett. 2001 Sep 17;11(18):2461-4. doi: 10.1016/s0960-894x(01)00466-8. Bioorg Med Chem Lett. 2001. PMID: 11549447 - The selectivity and potency of the new PDE5 inhibitor TPN729MA.
Wang Z, Zhu D, Yang X, Li J, Jiang X, Tian G, Terrett NK, Jin J, Wu H, He Q, Yang B, Shen J. Wang Z, et al. J Sex Med. 2013 Nov;10(11):2790-7. doi: 10.1111/jsm.12285. Epub 2013 Aug 12. J Sex Med. 2013. PMID: 23937247 - Review of phosphodiesterases in the urogenital system: new directions for therapeutic intervention.
Montorsi F, Corbin J, Phillips S. Montorsi F, et al. J Sex Med. 2004 Nov;1(3):322-36. doi: 10.1111/j.1743-6109.04047.x. J Sex Med. 2004. PMID: 16422964 Review. - [Phosphodiesterase 5--the enzyme inhibited by sildenafil (Viagra)].
Sandberg M, Natarajan V. Sandberg M, et al. Tidsskr Nor Laegeforen. 1999 Mar 10;119(7):945-9. Tidsskr Nor Laegeforen. 1999. PMID: 10210955 Review. Norwegian.
Cited by
- Production of Rhamnosyl Icariside II by snailase hydrolysis of Epimedium wushanense extracts.
Chen W, Liu G, Zhang Y. Chen W, et al. Heliyon. 2023 Dec 17;10(1):e23805. doi: 10.1016/j.heliyon.2023.e23805. eCollection 2024 Jan 15. Heliyon. 2023. PMID: 38192750 Free PMC article. - Preparation, Characterization, and In Vivo Evaluation of Amorphous Icaritin Nanoparticles Prepared by a Reactive Precipitation Technique.
Tang C, Meng K, Chen X, Yao H, Kong J, Li F, Yin H, Jin M, Liang H, Yuan Q. Tang C, et al. Molecules. 2021 May 14;26(10):2913. doi: 10.3390/molecules26102913. Molecules. 2021. PMID: 34068926 Free PMC article. - Inhibition of Phosphodiesterase 5 Promotes the Aromatase-Mediated Estrogen Biosynthesis in Osteoblastic Cells by Activation of cGMP/PKG/SHP2 Pathway.
Wisanwattana W, Wongkrajang K, Cao DY, Shi XK, Zhang ZH, Zhou ZY, Li F, Mei QG, Wang C, Suksamrarn A, Zhang GL, Wang F. Wisanwattana W, et al. Front Endocrinol (Lausanne). 2021 Mar 12;12:636784. doi: 10.3389/fendo.2021.636784. eCollection 2021. Front Endocrinol (Lausanne). 2021. PMID: 33776932 Free PMC article. - Exploration of icariin analog structure space reveals key features driving potent inhibition of human phosphodiesterase-5.
Chau Y, Li FS, Levsh O, Weng JK. Chau Y, et al. PLoS One. 2019 Sep 20;14(9):e0222803. doi: 10.1371/journal.pone.0222803. eCollection 2019. PLoS One. 2019. PMID: 31539416 Free PMC article. - Evaluation of selected traditional Chinese medical extracts for bone mineral density maintenance: A mechanistic study.
Rebhun JF, Du Q, Hood M, Guo H, Glynn KM, Cen H, Scholten JD, Tian F, Gui M, Li M, Zhao Y. Rebhun JF, et al. J Tradit Complement Med. 2018 Sep 29;9(3):227-235. doi: 10.1016/j.jtcme.2017.07.004. eCollection 2019 Jul. J Tradit Complement Med. 2018. PMID: 31193882 Free PMC article.
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Chemical Information
Miscellaneous