Some of the most promising leads for powerful therapeutic agents have arisen from marine sponges. Aside from providing an environmentally friendly avenue to these compounds, chemical synthesis enables the development of analogs with improved bioactivity and regularly leads to fundamental discoveries in chemistry, biology and medicine. The pyrrole-imidazole alkaloids are a diverse family of marine sponge derived natural products with reported bioactivity including: anticancer, antibiotic, antiviral, antihistiminic, antimuscarinic and potential leads for cystic fibrosis and Alzheimer's disease. This proposal encompasses both the chemical and biological aspects of several members of this natural product class, including its most complex members. Thus, enantioselective syntheses of sceptrin, oxysceptrin, nakamuric acid, ageliferin, nagelamide, axinellamine, massadine, and palau'amine are proposed. The overall aim is to provide useful amounts of these natural products using concise synthetic sequences and biomimetic cascade reactions. Upon achieving practical syntheses of these compounds we will study their structure activity relationships and mechanism of action through collaborations. The biological studies will be carried out in collaboration with leaders in the fields of cancer (Professor Bob Abraham, Burnham Institute), viral (Professor Raymond Schinazi, Emory), neuropharmacology (Professor George Siggins, Scripps) and physiology (Dr. Lee Sweeny, Penn State Med. Center). ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM073949-03
Application #
7254813
Study Section
Medicinal Chemistry Study Section (MCHA)
Program Officer
Schwab, John M
Project Start
2005-05-01
Project End
2010-04-30
Budget Start
2007-05-01
Budget End
2008-04-30
Support Year
3
Fiscal Year
2007
Total Cost
$277,517
Indirect Cost
Name
Scripps Research Institute
Department
Type
DUNS #
781613492
City
La Jolla
State
CA
Country
United States
Zip Code
92037
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