Three similar compounds isolated from marine sponges of the family Desmacididae that demonstrate anti-proliferative activity in vitro.
Cancer remains a major cause of illness, disability, and death. According to the World Health Organization, cancer is a leading cause of death worldwide, accounting for 8.2 million deaths in 2012.
Discorhabdin S, T, and U and their analogs have shown activity against cancer cell lines in vitro.
These compounds have a molecular structure that is distinct from other discorhabdins. They differ from each other only in the degree of saturation of the double bonds in the heteroaromatic rings. The inventors assessed anti-proliferative activity in human adenocarcinoma (A549), human pancreatic (PANC-1), and murine leukemia (P388) cell lines. Cells were cultured and then incubated with various concentrations of the test compounds. Results, determined by spectrophotometry, showed that these discorhabdins were effective in inhibiting the growth of cancer cells. The mechanism of action is unknown.
Only two published papers mention discorhabdin S, T, or U. One is authored by Gunsekera et al., and the other is below:
Bioorg Med Chem Lett. 2006 Apr 1;16(7):1944-6. Epub 2006 Jan 24.Semi-synthetic preparation of the rare, cytotoxic, deep-sea sourced sponge metabolites discorhabdins P and U.
Grkovic T, Kaur B, Webb VL, Copp BR.
Semi-synthetic routes to the enzyme inhibitory and potently anti-proliferative marine natural products discorhabdins P and U were developed by one-step methylation reactions of discorhabdins C and B, respectively. Two novel semi-synthetic derivatives of discorhabdin U were also prepared, one of which (6) exhibited significant anti-proliferative activity.
There remains a need for new and effective anticancer agents for humans and animals. Natural sources of biologically active compounds are yielding a growing number of effective therapeutic agents for various diseases. Using marine sponges as a source for new anticancer and antitumor agents expands the arsenal of available, effective, and novel therapeutic agents.
More effective antitumor and anticancer agents are needed. Only 66% of people with cancer will survive for at least 5 years, according to the National Cancer Institute so there is a great need for new anticancer agents. Although there may be some common characteristics among cancers and tumors, different types of tumors or cancers respond differently to the same therapy. An array of therapeutic compounds is needed in order to accommodate specific characteristics of particular tumor types or cancers. There is room in the market for new anti-proliferative compounds.
U.S. Patent 6,835,736 Issued Dec. 28, 2004.
Sarath P. Gunasekera , Ph.D. has been publishing in the field of natural products since 1973. Dr. Gunasekera is a scientist with the Harbor Branch Oceanographic’s Division of Biomedical Marine Research. His research interests include marine natural products chemistry with an emphasis on biologically active compounds having potential medicinal value. Current research focuses on the discovery of biologically active compounds from sponges and deep water microorganisms using enzymes that have potential as targets for therapeutic agents. Other interests include the chemical modification of biologically active compounds, examples: anti-cancer agent discodermolide and anti-inflammatory agents topsentins, for structure activity studies, and also, the use of high resolution NMR techniques for structure analysis. He has authored 96 publications and 21 patents.
Ross E. Longley, Ph.D. NPDDL Laboratory Director; Coordinator of Research Programs; Associate Professor of Microbiology and Immunology, Lake Erie College of Osteopathic Medicine-Bradenton FL. From 1984 to 1987, Dr. Longley was on the faculty at the University of Central Florida, Department of Biology, as an Assistant Professor to both undergraduate and graduate students of immunology and cancer biology. In 1987, he took the Group Leader position at the not-for-profit research organization Harbor Branch Oceanographic Institution. Dr. Longley’s team designed and implemented new screening assays for drug discovery and mechanism of action work in the Immunology and Cancer Research Program. For the next 15 years, under his direction, his laboratory discovered potential anti-cancer agents in marine natural products. In 1992 and again in 1997, he was awarded grants from the National Cancer Institute for the detection of anti-cancer agents found in marine organisms. Thanks to Dr. Longley’s research, the compound discodermolide was discovered and subsequently licensed in 1998 by Novartis pharmaceutical company. Discodermolide is presently in clinical trial as a new anti-cancer agent. After 15 years with Harbor Branch, Dr. Longley joined Taxolog, Inc., in May 2002.Dr. Longley’s research (2007) included taxane drug discovery, assay development, molecular and cellular immunology, tumor biology, flow cytometric methods for analysis of apoptosis and cell cycle-mediated events, mechanism of action studies of taxane derivatives and confocal microscopy methodology for mechanism of action studies.
Shirley A. Pomponi, Ph.D. In addition to directing the Division of Biomedical Marine Research, Dr. Pomponi leads the Marine Invertebrate Cell Culture Program. A major emphasis of her research is on the development of methods for sustainable use of marine resources for drug discovery and development. Research is focused on establishing cell lines of marine sponges that can be used as models to study production of sponge-derived bioactive metabolites and the factors which control expression of production. Dr. Pomponi discovered a chemical that can kill cancer cells, called discodermolide.
Amy Wright, Ph.D. Director, Research Professor, Harbor Branch Oceanographic at Florida Atlantic University. Currently on the faculty of the Medical University of South Carolina in the Marine Biomedicine and Environmental Sciences department. Dr. Wright has conducted research in the field of natural products chemistry. Her research focuses on the discovery of compounds with utility in the treatment of cancer and infectious disease. She has published approximately 60 articles and is an author on 34 patents.
Oncology, Drug discovery
BrochureDiscorhabdin compounds and methods of use
Patent Number | US6835736 |
Patent Status | Issued |
Issue Date | December 28, 2004 |