Marine-Derived Compounds with Anti-Tumor

and Anti-Fungal Activities

Application

Lasonides C, D, E, F - active marine-derived macrolide compounds - show anti-cell proliferative activities in vitro that could be use primarily in the treatment of cancer also in the treatment of multi-drug resistant cancer cells, secondarily in the treatment of fungal infections preferably in mammal then for the control of fungi growth in spoilage of food, in cosmetic and other consumer items.

Problem

1/ In 2014, about 1,665,540 new cancer cases are expected to be diagnosed in the U.S. and about 585,720 are expected to die of cancer, almost 1,600 people per day. Cancer is the second most common cause of death in the US. Cancer is characterized by an accelerated and uncontrolled multiplication of a set of aberrant cells, which lose their apoptotic ability. While certain methods and chemical compositions have been developed which aid in inhibiting, remitting, or controlling the growth of, for example, tumors, new methods and antitumor chemical compositions are needed, as well as in multi-drug resistance (MDR).

2/ Infestations in humans, animals and plants have increased, with many having lethal consequences. There are growing needs amongst others in controlling fungi. Fungi are highly resistant microbiological eukaryotic microorganisms. On the one hand, increased use of antibiotics and immunosuppressive drugs are major factors contributing to higher frequency of fungal infections in immunocompromised patients. One the other hand, chemical fungicides have raised environmental and safety concerns (oncogenic nature, teratogenic effects on human and soil pollution) and the regulation of food safety has become more stringent for avoiding food poisoning. While certain methods and chemical compositions have been developed that aid in inhibiting or controlling the growth of fungi, new methods and new effective antifungal compounds or compositions are needed.

Technology

The technology is a bioassay-guided fractionation of an extract that led to the isolation of four structurally different compounds, lasonolides C, D, E and F from an ocean sponge, Forcepia triabilis. These compounds are biologically active macrolides with anti-cell proliferation activities that show utility in inhibiting cancer cells and fungal growth.

The inventors have shown that lasonolides C, D, E and F have potent anti-tumor activities. It extends to the compositions with these compounds, their enantiomeric forms in excess, their analogues and their derived-salts. Furthermore, lasonolide compounds C and F have potent anti-fungal activities. Lasonolides C, D, E and F are useful for inhibiting pathological cellular proliferation in primary end-use of the treatment of cancer as well as in the treatment of multi-drug resistant cancer cells, secondary in the treatment of fungal infections, particularly lasonolides C and F, preferably in mammal then for the control of fungi growth in spoilage of food, in cosmetic and other consumer items.

As example, lasonolides C, D, E have cytotoxic activities on tumoral cells candidates (A549 human lung adenocarcinoma, PANC-1 human pancreatic cancer and NCI-ADR RES ) with IC50 values from 0.12µM to >8µM). Also, against a fungi candidate, Candida albicans, lasonolides C and F reach their minimum inhibitory concentration (MIC) respectively at 5µg/ml and 50µg/ml.

Competitive Advantage

This is a sustaining technology that brings great value by offering a natural alternative for the control of fungi and for the treatment of the multi-drug resistance (MDR) or multidrug resistance-associated protein (MRP) cases.

The primary field of use of the technology is the treatment of cancer, as well as the treatment of multi-drug resistant cancer cells. The expansion of new drugs in oncology represents one of the most promising objectives of the pharmaceutical industry. Indeed, across 2013, 15 new molecular entities were approved by the FDA; out of which seven were for oncology. Currently targeted therapies dominate the oncology pipeline, followed by chemotherapy. The market landscape is highly competitive; however, the need for novel anti-tumor compounds is high.

The secondary field of use is in the development of antifungal products: - Preferably in mammal. The U.S. human antifungal therapeutics market reached nearly $4.9 billion in 2013. It is projected to grow to $5.5 billion in 2018; - Then for the control of fungi growth in spoilage of food, in cosmetic and other consumer items. The demand particularly for food safety products in the U.S. is forecast to increase of 7.3 percent annually to $4.5 billion in 2016.

Patent Status

U.S. Patent US 7,521,474 B2 Biologically Active Lasonolide Compounds Issued on April 21st, 2009.

Researchers

Amy E. Wright, Ph.D. (UC, Riverside) is Research Professor and Director of the Center for Marine Biomedical and Biotechnology Research at Harbor Branch Oceanographic Institute, Florida Atlantic University. She has conducted research, for the past 25 years, in the field of natural products chemistry. Her primary research interests focus on the purification and structure identification of naturally occurring compounds, which may have utility in treating cancer. Over the course of her career, her research group has identified over 100 different marine natural products with biological activity. One compound she identified early in her career has been approved in Europe for the treatment of soft tissue sarcoma.

Shirley A. Pomponi, Ph.D. (University of Miami) is Research Professor and Executive Director of the NOAA Cooperative Institute for Ocean Exploration, Research, and Technology at Harbor Branch Oceanographic Institute, Florida Atlantic University. Her research focuses on marine biotechnology, in general, and sponge systematics, cell and molecular biology, in particular.

Peter J. McCarthy, Ph.D. (University of Kent, Canterbury, UK) is Research Professor at the Center for Marine Biomedical and Biotechnology Research, Harbor Branch Oceanographic Institute, Florida Atlantic University. His research focuses on the discovery of novel natural products and enzymes produced by heterotrophic marine-derived microorganisms.

Ross E. Longleya, Ph.D. (University of Oklahoma) is Senior Vice President of Preclinical Research and Development of Taxolog, Inc. He has been Group Leader for Harbor Branch Oceanographic Institution since 1987. His 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.

Ying Chen, M.S. (Fudan of Science and Technology and Academia Sinica, China) is Senior Analytical Chemist at Boston Analytical Inc and was Research Associate for Ocean Exploration, Research, and Technology at Harbor Branch Oceanographic Institute, Florida Atlantic University.

Field

Oncology, Fungal infection, Food microbiology