Historically natural products from terrestrial plants and microbes have provided humankind with some of our most novel and valued treatments for infectious diseases, in addition to providing new targets for the rational design of synthetic drugs. The key objectives to be addressed by this project include: 1. The characterization of novel marine natural product leads for the treatment of HIV-1 and AIDS OI from marine invertebrates, algae and microbes. This involves the bioassay guided isolation of active extracts to be accomplished utilizing several significant AIDS OI including C. albicans, C. neoformans, S. aureus, MRS and Mtb. Marine samples will be identified and dereplicated using a combination of traditional taxonomic techniques combined with molecular biology, secondary metabolism and database analysis. Purified natural products will be examined for activity against both wild type and resistant strains of HIV-1 and AIDS OI. Structure determination will be completed using spectroscopic methods utilized in combination with molecular modeling and chemical methods. In particular detailed high field NMR studies will be completed for noncrystalline materials and X-ray crystallography will be utilized for materials that can successfully be crystallized. 2. The optimization of marine natural product leads identified in aim 1 will be completed using semisynthesis and biotransformation studies. The rational modification of marine products will be based on a combination of SAR for the structural class, antiinfective activity and a statistical analysis of pharmacophores found in clinically utilized drugs. Materials will be sourced through well established relationships with academic programs in Indonesia, Jamaica, Egypt, Saudi Arabia, and Nigeria in addition to the evaluation of domestic samples. These areas broadly represent the greatest marine biodiversity available on the planet and a well organized repository of crude extracts, initial column fractions as well as pure natural, semisynthetic and synthetic products will be maintained for future evaluation against emerging or remerging/resistant infectious diseases.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI036596-10
Application #
6872187
Study Section
Special Emphasis Panel (ZRG1-AARR-E (03))
Program Officer
Lambros, Chris
Project Start
1995-04-01
Project End
2008-05-31
Budget Start
2005-06-01
Budget End
2006-05-31
Support Year
10
Fiscal Year
2005
Total Cost
$354,835
Indirect Cost
Name
University of Mississippi
Department
Pharmacology
Type
Schools of Pharmacy
DUNS #
067713560
City
University
State
MS
Country
United States
Zip Code
38677
Gogineni, Vedanjali; Hamann, Mark T (2018) Marine natural product peptides with therapeutic potential: Chemistry, biosynthesis, and pharmacology. Biochim Biophys Acta Gen Subj 1862:81-196
Wang, Bin; Waters, Amanda L; Valeriote, Frederick A et al. (2015) An efficient and cost-effective approach to kahalalide F N-terminal modifications using a nuisance algal bloom of Bryopsis pennata. Biochim Biophys Acta 1850:1849-54
Kasanah, Noer; Farr, Lorelei Lucas; Gholipour, Abbas et al. (2014) Metabolism and resistance of Fusarium spp. to the manzamine alkaloids via a putative retro pictet-spengler reaction and utility of the rational design of antimalarial and antifungal agents. Mar Biotechnol (NY) 16:412-22
Li, Huayue; Su, Mingzhi; Hamann, Mark T et al. (2014) Solution structure of a sponge-derived cystine knot peptide and its notable stability. J Nat Prod 77:304-10
Waters, Amanda L; Peraud, Olivier; Kasanah, Noer et al. (2014) An analysis of the sponge Acanthostrongylophora igens' microbiome yields an actinomycete that produces the natural product manzamine A. Front Mar Sci 1:
Li, Huayue; Bowling, John J; Fronczek, Frank R et al. (2013) Asteropsin A: an unusual cystine-crosslinked peptide from porifera enhances neuronal Ca2+ influx. Biochim Biophys Acta 1830:2591-9
Olugbuyiro, J A O; Moody, J O; Hamann, M T (2013) Phytosterols from Spondias mombin Linn with Antimycobacterial Activities. Afr J Biomed Res 16:19-24
Hwang, In Hyun; Oh, Joonseok; Kochanowska-Karamyan, Anna et al. (2013) A novel natural phenyl alkene with cytotoxic activity. Tetrahedron Lett 54:3872-3876
Zou, Yike; Hamann, Mark T (2013) Atkamine: a new pyrroloiminoquinone scaffold from the cold water Aleutian Islands Latrunculia sponge. Org Lett 15:1516-9
Wahba, Amir E; Fromentin, Yann; Zou, Yike et al. (2012) Acantholactone, a new manzamine related alkaloid with an unprecedented ?-lactone and ?-lactam ring system. Tetrahedron Lett 53:6329-6331

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