Grantee Research Project Results
Final Report: Application of Green Technology in the Production of Pharmaceuticals
EPA Grant Number: SU836033Title: Application of Green Technology in the Production of Pharmaceuticals
Investigators: Manning, Thomas J. , Phillips, Dennis , Wylie, Greg , Nienow, James , Baum, Jeramy , Ledwitch, Kaitlyn , Ogburn, Ryenne
Institution: Valdosta State University , University of Georgia
EPA Project Officer: Hahn, Intaek
Phase: I
Project Period: August 15, 2011 through August 14, 2012
Project Amount: $14,900
RFA: P3 Awards: A National Student Design Competition for Sustainability Focusing on People, Prosperity and the Planet (2011) RFA Text | Recipients Lists
Research Category: P3 Challenge Area - Sustainable and Healthy Communities , P3 Challenge Area - Chemical Safety , Pollution Prevention/Sustainable Development , P3 Awards , Sustainable and Healthy Communities
Objective:
Our project, which evolved with time, is broken into three phases or three sub-projects. Each of these sub-projects is innovative to the point we have filed patent applications and have prepared and published papers in peer reviewed scientific journals. The sub-projects are:
Green Synthesis. Our group developed a novel method to produce bryostatin, a well-known Alzheimer’s and cancer drug. We call our technique pharmaceutical aquaculture. It is essentially a green method of farming the ocean. Bryostatin-1 (C47H68O17), a large macrolid, is produced by marine bacteria that are symbiotic with the bryozoan Bugula neritina. It is extremely difficult for organic chemists to synthesize in the lab. Genetics attempting to move genes from the marine bacteria to common bacteria such as E. Coli have failed. Because the current method still depends on harvesting Bugula and extracting the drug at a very low yield (10-7%), the cost of bryostatin is several million dollars per gram. We have produced gram quantities of low purity material using our approach
We also have preliminary results that show we can maintain marine microbes in cotton balls. The balls are soaked in ocean water, treated with the proper nutrients and, left out on a counter by themselves, maintain ocean life for up to thirty days (this is the longest we have checked so far).
Remote Operated Vehicles (ROV). Our green synthesis approach is focused on sediment. Our model holds that the symbiotic bacterium that produces bryostatin actually resides in marine sediment with a specific chemical signature. We designed, built and tested several generations of low cost ROV’s to operate in murky, cold environments and collect samples. This approach eliminates the tremendous problem of by-catch currently encountered when Bugula collectors use shrimp nets to harvest the bryozoan.
Delivery: With our field research in the ocean, we often found bryostatin in mineral rich environments. Likewise, it was common for use to find bryostatin bound to iron cations (i.e. Fe-bryostatin). Bryostatin, like many other drugs, has a low solubility in water. We found that binding it to a cation raises it water solubility. We extended this work to copper ions and drugs containing amines. Submitting samples to the National Cancer Institute’s 60 cell line panel, we found that copper, when bound to known and well-studied cancer drugs, increases their efficacy. Compared to other platforms for drug delivery (i.e. liposomes, nanoparticles, proteins, etc.), they are real chemical and green technology advantages to our approach.
In addition to the research, a class developed a poster series (four 4 ft. by 5 ft. posters) that feature the World Health Organization’s list of essential drugs. While many environmental projects focus on clean water in third world countries, we are focusing on improving the delivery of these drugs. Almost one half of the WHO list of essential medicines contains nitrogen. Five research students are currently modeling the impact that binding these drugs to copper (II) will have on their water/physiological solubility.
Summary/Accomplishments (Outputs/Outcomes):
To outline the highlights or new knowledge developed as part of this project:
Using our green technology approach, we have used our process to produce bryostatins. In addition to developing a green synthesis approach, we use cotton to extract the drug from the growth medium. In the same method that dyes stick to cotton, so do the drugs we are harvesting. This eliminates costly and toxic solvents.
At a trace level, we have produced taxol and ET743 using our green approach.
We have developed and tested the copper(II) cation as a platform for drug delivery. The National Cancer Institute tested two of our prototypes (Cu-taxol; Cu-quinine). Cu-taxol outperformed taxol in 52 out of 60 cell lines. They are now being considered for testing against leukemia and pancreatic cancer. We are currently performing computational work on approximately 140 drugs listed on the World Health organization’s list of essential medicines that contain nitrogen atom to evaluate if their efficacy can be improved by binding to the copper ion.
We have designed, built and tested ROV’s to collect sediment samples from the ocean.
We have filed two utility patent applications, have one paper published and a second in preparation and have given over a dozen presentations at meetings (by April 17th, 2012).
Conclusions:
To date our project has been successful. Like most research projects, our topic evolved with certain successes and failures. The central point in this project is the green synthesis of natural products, using bryostatin as a prototype. We’ve had three central students each leading their specific groups. These sub-groups of undergraduate students have ranged in size from three to five students. We have also involved a class in this work and given a number of talks at scientific meetings.
Both the success and novelty of our project is emphasized by the recent filing of two Untied States patent applications, the acceptance of a paper in a peer reviewed journal and the National Cancer Institute accepting our drugs for testing and further evaluation.
Journal Articles on this Report : 2 Displayed | Download in RIS Format
| Other project views: | All 4 publications | 2 publications in selected types | All 2 journal articles |
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Manning TJ, Phillips D, Wylie G, Bythell B, Clark S, Ogburn R, Ledwitch K, Collis C, Patterson S, Lasseter L. Copper ion as a delivery platform for taxanes and taxane complexes. Bioorganic & Medicinal Chemistry Letters 2014;24(1):371-377. |
SU836033 (Final) |
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Manning T, Ogburn R, Ledwitch K, Wylie G, Phillips D. Structural studies of the copper(II)-quinine complexes. Florida Scientist 2012;75(1):51-62. |
SU836033 (Final) |
Exit Exit |
Supplemental Keywords:
green technology, aquaculture, marine natural products, bryostatinRelevant Websites:
YouTube: FINAL EXAM Z2MARINE Exit
YouTube: marine chem project Exit
YouTube: Friday in Fiesta Key Exit
YouTube: VSU Marine Chemistry in the Florida Keys Exit
YouTube: Marine Chemistry Exit
YouTube: Spring Break 2011 Valdosta State University Marine Chem Final Exit
YouTube: Marine Chem Trip to Keys 2011 Exit
YouTube: Marine Chemistry Keys Trip 2011 Exit
YouTube: marine chem video final Exit
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YouTube: Marricco and Ashlee Marine Chem Video Exit
The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Conclusions drawn by the principal investigators have not been reviewed by the Agency.