Cancer, autoimmune conditions, and inflammatory diseases continue to affect millions of humans and animals. New therapies are needed to combat cancers, organ rejection, diabetes, lupus, meningitis, Parkinson’s disease, Alzheimer’s disease, ALS, and more.

Technology

Assays of two new linderazulene compounds showed inhibition of undesirable cell proliferation. Cell proliferation associated with autoimmune disorders, inflammation, tumors, and cancer are included in the claims by the inventors.

11-carbomethoxylinderazulene (I) and 11-formylinderazulene (II) were extracted from a soft coral found off the northwest coast of Curacao, using the Harbor Branch Oceanographic Institution’s Johnson-Sea-Link research submersible to gather samples. Samples were purified and concentrated using common procedures. Human pancreatic cells (PANC-1) and murine leukemia cells (P388) were used to test the anti-proliferative effects of the linderazulenes. Results were obtained by spectrophotometry. The mechanism of action was not investigated.

Competitive Advantage

The linderazulenes claimed are novel compositions that are useful for an array of disorders and diseases, including cancers. Analogs and salts are also included in the patent. With the possibility of therapeutic effectiveness in more than one disease, the odds of producing a successful pharmaceutical are increased. The compounds can be formulated according to common methods. Only four papers in the literature discuss linderazulenes:

1: Chen M, Han L, Wang Y, Zhang XL, Wang CY. A new sesquiterpene from the Hainan gorgonian Menella kanisa Grassoff. Nat Prod Res. 2014;28(15):1147-51. doi:10.1080/14786419.2014.918122.

2: Pénez N, Culioli G, Pérez T, Briand JF, Thomas OP, Blache Y. Antifouling properties of simple indole and purine alkaloids from the Mediterranean gorgonian Paramuricea clavata. J Nat Prod. 2011 Oct 28;74(10):2304-8. doi:10.1021/np200537v.

3: Reddy NS, Reed JK, Longley RE, Wright AE. Two new cytotoxic linderazulenes from a deep-sea gorgonian of the genus Paramuricea. J Nat Prod. 2005 Feb;68(2):248-50.

4: Sakemi S, Higa T. 2,3-Dihydrolinderazulene, a new bioactive azulene pigment from the gorgonian Acalycigorgia sp. Experientia. 1987 Jun 15;43(6):624-5.

The unmet need for effective treatments for cancers and tumors, autoimmune disorders, and inflammation is huge and continues to grow with the population. In 2012, autoimmune diseases affected approximately 23.5 M people in the U.S. according to the NIH. New cases of cancer in the U.S. were over 1.6M in 2014 with 40% of the population predicted to be diagnosed with cancer at some point in the life. Inflammatory diseases cover the range body systems, from digestive to connective tissue to glandular.

Stage of Development

Two compounds.
Assays of anti-proliferative activity in cancer cell lines.

Patent Status

U.S. Patent 6,852,754 Issued February 8, 2005.

Researchers

Amy E. 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.

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.

Srinivasa Reddy Natala Ph.D. has been an author on 7 issued patents, six of which are assigned to Takeda. He was active in the development of TAK960, an anticancer agent from Takeda that is in Phase I trials (2013).

John K. Reed Ph.D. is a Senior Scientist with the Division of Biomedical Marine Research at Harbor Branch Oceanographic Institution. On that website he states: Our work at the Division of Biomedical Marine Research has led to the discovery of many new chemical compounds that may have potential in the treatment of various human diseases. One is now in clinical trials for the treatment of breast cancer. After 15 years of research, we are very hopeful that this will provide a new cure for breast cancer. We recently received a $1 million grant to discover a new treatment for pancreatic cancer. During this NOAA mission to the Gulf of Mexico, we will collect new species and certainly hope to discover novel chemicals that could provide that cure.