The UF-patented compound, largazole, is derived from cyanobacteria that grow on coral reefs. Researchers, who described results from early studies today (Aug. 7) at an international natural products scientific meeting in Athens, Greece, say it is one of the most promising they've found since the college's marine natural products laboratory was established three years ago.
An initial set of papers in the Journal of the American Chemical Society also has garnered the attention of other scientists, and the lab is racing to complete additional research. The molecule's natural chemical structure and ability to inhibit cancer cell growth were first described in the journal in February and the laboratory synthesis and description of the molecular basis for its anticancer activity appeared July 2.
"It's exciting because we've found a compound in nature that may one day surpass a currently marketed drug or could become the structural template for rationally designed drugs with improved selectivity," said Hendrik Luesch, Ph.D., an assistant professor in UF's department of medicinal chemistry and the study's principal investigator.
Largazole, discovered and named by Luesch for its Florida location and structural features, seeks out a family of enzymes called histone deacetylase, or HDAC. Overactivity of certain HDACs has been associated with several cancers such as prostate and colon tumors, and inhibiting HDACs can activate tumor-suppressor genes that have been silenced in these cancers.
Although scientists have been probing the depths of the ocean for marine products since the early 1960s, many pharmaceutical companies lost interest before researchers could deliver useful compounds because natural products were considered too costly and time-consuming to research and develop.
Many common medications, from pain relievers to cholesterol-reducing statins, stem from natural products that grow on the earth, but there is literally an ocean of compounds yet to be discovered in our seas. Only 14 marine natural products developed are in clinical trials today, Luesch said, and one drug recently approved in Europe is the first-ever marine-derived anticancer agent.
"Marine study is in its infancy," said William Fenical, Ph.D., a distinguished professor of oceanography and pharmaceutical sciences at the University of California, San Diego. "The ocean is a genetically distinct environment and the single, most diverse source of new molecules to be discovered."
The history of pharmacy traces its roots back thousands of years to plants growing on Earth's continents, used by ancient civilizations for medicinal purposes, Fenical added. Yet only in the past 30 years have scientists begun to explore the organisms in Earth's oceans, he said. Fewer than 30 labs exist worldwide and research dollars have only become available in the past 15 years.
HDACs are already targeted by a drug approved for cutaneous T-cell lymphoma manufactured by the global pharmaceutical company Merck & Co. Inc. However, UF's compound does not inhibit all HDACs equally, meaning a largazole-based drug might result in improved therapies and fewer side effects, Luesch said.
Since 2006, Luesch and his team of researchers have screened cyanobacteria provided by collaborator Valerie Paul, Ph.D., head scientist at the Smithsonian Marine Station in Fort Pierce. They check the samples for toxic activity against cancer cells and last year encountered one exceptionally potent extract — the one that ultimately yielded largazole.
To conduct further biological testing on the compound, Luesch and his team have been collaborating with Jiyong Hong, an assistant professor in the department of chemistry at Duke University, to replicate its natural structure and its actions in the laboratory.
Luesch said that within the next few months he plans to study whether largazole reduces or prevents tumor growth in mice.
Luesch has several other antitumor natural products from Atlantic and Pacific cyanobacteria in the pipeline.
"We have only scratched the surface of the chemical diversity in the ocean," Luesch said. "The opportunities for marine drug discovery are spectacular."
Linda Homewood | EurekAlert!
Researchers find new mutation in the leptin gene
24.06.2019 | Texas Biomedical Research Institute
Straight to the heart
24.06.2019 | Max-Delbrück-Centrum für Molekulare Medizin in der Helmholtz-Gemeinschaft
From June 25th to 27th 2019, the Fraunhofer Institute for Digital Media Technology IDMT in Ilmenau (Germany) will be presenting a new solution for acoustic quality inspection allowing contact-free, non-destructive testing of manufactured parts and components. The method which has reached Technology Readiness Level 6 already, is currently being successfully tested in practical use together with a number of industrial partners.
Reducing machine downtime, manufacturing defects, and excessive scrap
The quality of additively manufactured components depends not only on the manufacturing process, but also on the inline process control. The process control ensures a reliable coating process because it detects deviations from the target geometry immediately. At LASER World of PHOTONICS 2019, the Fraunhofer Institute for Laser Technology ILT will be demonstrating how well bi-directional sensor technology can already be used for Laser Material Deposition (LMD) in combination with commercial optics at booth A2.431.
Fraunhofer ILT has been developing optical sensor technology specifically for production measurement technology for around 10 years. In particular, its »bd-1«...
The well-known representation of chemical elements is just one example of how objects can be arranged and classified
The periodic table of elements that most chemistry books depict is only one special case. This tabular overview of the chemical elements, which goes back to...
Light can be used not only to measure materials’ properties, but also to change them. Especially interesting are those cases in which the function of a material can be modified, such as its ability to conduct electricity or to store information in its magnetic state. A team led by Andrea Cavalleri from the Max Planck Institute for the Structure and Dynamics of Matter in Hamburg used terahertz frequency light pulses to transform a non-ferroelectric material into a ferroelectric one.
Ferroelectricity is a state in which the constituent lattice “looks” in one specific direction, forming a macroscopic electrical polarisation. The ability to...
Researchers at TU Graz calculate the most accurate gravity field determination of the Earth using 1.16 billion satellite measurements. This yields valuable knowledge for climate research.
The Earth’s gravity fluctuates from place to place. Geodesists use this phenomenon to observe geodynamic and climatological processes. Using...
24.06.2019 | Event News
29.04.2019 | Event News
17.04.2019 | Event News
24.06.2019 | Event News
24.06.2019 | Agricultural and Forestry Science
24.06.2019 | Life Sciences