Next Article in Journal
Zoanthamine Alkaloids from the Zoantharian Zoanthus cf. pulchellus and Their Effects in Neuroinflammation
Previous Article in Journal
(−)-Homosalinosporamide A and Its Mode of Proteasome Inhibition: An X-ray Crystallographic Study
Article Menu
Issue 7 (July) cover image

Export Article

Open AccessArticle
Mar. Drugs 2018, 16(7), 241;

Preclinical Evaluation of Discorhabdins in Antiangiogenic and Antitumor Models

Molecular Pharmacology Section, Genitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
Department of Chemistry, Chemistry Research Laboratory, University of Oxford, Oxford OX1 5JJ, UK
School of Chemical Sciences, University of Auckland, Auckland 1142, New Zealand
Molecular Targets Program, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA
Author to whom correspondence should be addressed.
Received: 20 June 2018 / Revised: 9 July 2018 / Accepted: 16 July 2018 / Published: 19 July 2018
Full-Text   |   PDF [5197 KB, uploaded 19 July 2018]   |  


Elements of the hypoxia inducible factor (HIF) transcriptional system, a key regulator of the cellular hypoxic response, are up-regulated in a range of cancer cells. HIF is fundamentally involved in tumor angiogenesis, invasion, and energy metabolism. Inhibition of the transcriptional activity of HIF may be of therapeutic benefit to cancer patients. We recently described the identification of two marine pyrroloiminoquinone alkaloids with potent activity in inhibiting the interaction between the oncogenic transcription factor HIF-1α and the coactivator protein p300. Herein, we present further characterization data for these two screening hits: discorhabdin H (1) and discorhabdin L (2), with a specific focus on their anti-angiogenic and anti-tumor effects. We demonstrated that only discorhabdin L (2) possesses excellent anti-angiogenic activity in inhibiting endothelial cell proliferation and tube formation, as well as decreasing microvessel outgrowth in the ex vivo rat aortic ring assay. We further showed that discorhabdin L (2) significantly inhibits in vivo prostate tumor growth in a LNCaP xenograft model. In conclusion, our findings suggest that discorhabdin L (2) represents a promising HIF-1α inhibitor worthy of further drug development. View Full-Text
Keywords: discorhabdins; hypoxia; HIF; angiogenesis; marine natural products; alkaloids discorhabdins; hypoxia; HIF; angiogenesis; marine natural products; alkaloids

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

Share & Cite This Article

MDPI and ACS Style

Harris, E.M.; Strope, J.D.; Beedie, S.L.; Huang, P.A.; Goey, A.K.L.; Cook, K.M.; Schofield, C.J.; Chau, C.H.; Cadelis, M.M.; Copp, B.R.; Gustafson, K.R.; Figg, W.D. Preclinical Evaluation of Discorhabdins in Antiangiogenic and Antitumor Models. Mar. Drugs 2018, 16, 241.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics



[Return to top]
Mar. Drugs EISSN 1660-3397 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top