About
The Center for Drug Discovery was established to provide the environment necessary to focus on and develop a wide variety of unique research concepts pioneered by Nicholas Bodor. Dr. Bodor has introduced revolutionary, general and comprehensive drug design concepts known as retrometabolic design approaches. These concepts strategically combine chemical and enzymatic (metabolic) processes to achieve drug targeting and to produce safe drugs and environmental chemicals. At the opposite end of the retrometabolic design loop are the chemical drug targeting systems (CDS) and the soft drugs (SD). A CDS is inactive by design and is enzymatically activated stepwise to produce the active drug only (or preferentially) at the target site/organ. Animal and human trials have demonstrated the safety and usefulness of the unique targeting system (redox CDS) for the potential treatment of Alzheimer’s disease, stroke and hormonal disturbances. Similar redox systems for brain targeting of neurotransmitters, antiviral and antiretroviral agents, antibiotics, antitumor, anti, anti-inflammatory drugs, etc., for the potential safe treatment of epilepsy, Parkinson’s disease, AIDS-related dementia, encephalitis, etc., were also introduced by Dr. Bodor and researched at the Center for Drug Discovery. The first successful brain targeting-delivery of neuropeptides was accomplished by Dr. Bodor’s research group, combining the redox targetor with strategically selected amino acid “spacers” and large lipophilic surrounding (cholesterol) called “molecular packaging” and “sequential metabolism,” a general method which, after its first publication in Science, was highlighted by Harvard Health Letters as one of the top ten discoveries of 1992.
Dr. Bodor’s approach is unique in covering the various complex fields related to drug design and development, and has carried a number of these concepts through their final application.
The design concepts incorporated in the soft drug approaches were used by Dr. Bodor to develop a general and comprehensive program, including a computerized, expert system which can be used to design all potential and possible metabolites and the corresponding safe active soft drugs and chemical delivery systems. During this design process, novel methods to calculate and predict molecular properties such as partition coefficients, molecular volume, surface, etc., were developed by Dr. Bodor. As a most recent development, a new method, the predict rates of enzymatic hydrolysis by human esterases was developed based on an initially novel concept, incorporating calculated molecular volumes and electronic and steric properties. In collaboration with Dr. Peter Buchwald, a computer program was developed, which was licensed by UFRF to a drug design technology company.
A comprehensive description of the above concepts can be found in N. Bodor and P. Buchwald, “Retrometabolism-Based Drug Design and Targeting,” in Burger’s Medicinal Chemistry, 6th Edition, John Wiley & Sons, Ed. D. Abraham.
The development of these and other unique concepts have required a focused research group and specialized instrumentation that cannot be provided within a department. The Center for Drug Discovery was established and continues to function to further these innovative approaches and bring them to their optimal results.
Mission
The Center for Drug Discovery was established to provide a strong multidisciplinary approach to research involving faculty members in the Department of Pharmaceutics in the College of Pharmacy, the Division of Endocrinology and Metabolism and the Division of Infectious Disease in the Department of Medicine, College of Medicine, and the VA Hospital at the University of Florida in Gainesville. Important components of the Center include a computer-assisted drug design group, an electrophysiological laboratory, a histopathology laboratory, as well as synthetic analytical pharmacokinetic and pharmacodynamic programs.
Current collaborators include faculty and/or research scientists from the Depatment of Pharmaceutics, Department of Chemistry, Department of Ophthalmology of the University of Florida, Center for Organ Transplant, University of Miami, Institute for Drug Research, Budapest, Hungary, University of Iceland, Jannsen Pharmaceutical Comp., Teva Pharmacutical Company, Alchem Laboratories, and others.
Research
The focus has been on general methods for targeting (differential delivery) of a variety of drugs (antiviral, anticancer, antiinflammatory and antidementia agents, gonadal steroids for central control of biological processes, etc.) into the central nervous system (chemical delivery systems). Recently, brain-targeting of neuropeptides has been developed. Chemical targeting (delivery) systems also have been designed and evaluated for ophthalmic use (potential safe treatment of glaucoma). Studies on the general "soft drug" concept (the opposite end of the chemical delivery systems in the retrometabolic design) involve soft analogs for anticholinergics and inactive metabolite-based soft drugs (steroids, beta-blockers).
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Last modified October 16, 2006
