This research venture aims to explore Puerto Rican marine biodiversity as a means to discover new and improved anti-cancer and anti-microbial drug candidates, and further seeks to develop these drug candidates into commercially acceptable therapeutics, with the capacity to manage and treat cancers as well as infectious diseases, and contribute to global health care. Marine invertebrates have been identified for a long time as likely sources of new biomedicinal substances. Pharmacologists, physiologists and biochemists have demonstrated that many of these novel marine products modify fundamental life processes in ways suggesting biomedical applications. These molecules can serve as leads to guide the pharmaceutical and chemical industries in developing new products. Our proposed research aims specifically at Puerto Rican marine invertebrates (sponges, gorgonian corals, mollusks, and ascidians) as a likely resource for novel anti- cancer and anti-microbial natural products. Since less than 1% of the species of marine invertebrates known to exist near Puerto Rico have been assessed chemically for their secondary metabolite composition, and many of these have been shown to produce metabolites possessing potent chemotherapeutic properties, organisms from this region have the potential to contain a wealth of novel drugs. Specifically, during the four years of this research we plan to carefully scrutinize the pharmacology and chemistry of 350 representative species belonging to four major Caribbean phyla. Initial extraction with solvents of different polarities (e.g., hexane, methylene chloride, and methanol) will be monitored using cytotoxicity and anti-microbial activity assays. Only extract residues possessing strong cytotoxic and anti-microbial properties will be screened further for chemical structural features by HPLC/ESI-MS and NMR spectroscopy. Further purification by chromatography (column, GC, LC) and determination of molecular structure will proceed if warranted by the screening results. Structure elucidation will rely heavily on spectral methods (e.g., 1H and 13C NMR, MS, IR, UV) and X-ray diffraction techniques. Candidate compounds will be scheduled for clinical trial to assess their clinical potential. By determining the chemical structures and, eventually, the biochemical pathways by which these compounds are produced and the environmental or physiological triggers controlling their production, techniques of enhanced commercial production can be developed.

Public Health Relevance

In the USA alone over 1.4 million new cancer cases are expected to be diagnosed in 2008. Current epidemiological evidence suggests that every year HIV/AIDS, malaria, and tuberculosis account for over 9 million deaths worldwide. Our research program aims to explore marine invertebrate biodiversity as a means to discover new and improved anti-cancer and anti-infective drug candidates, and further seeks to develop these drug candidates into commercially acceptable therapeutics, with the capacity to manage and treat these diseases, thus contributing to global health care.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Enhancement Award (SC1)
Project #
5SC1GM086271-04
Application #
8436228
Study Section
Special Emphasis Panel (ZGM1-MBRS-X (CH))
Program Officer
Lees, Robert G
Project Start
2010-03-01
Project End
2015-02-28
Budget Start
2013-03-01
Budget End
2015-02-28
Support Year
4
Fiscal Year
2013
Total Cost
$284,694
Indirect Cost
$93,624
Name
University of Puerto Rico Rio Piedras
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
143960193
City
San Juan
State
PR
Country
United States
Zip Code
00931
Jimenez-Romero, Carlos; Mayer, Alejandro M S; Rodriguez, Abimael D (2014) Dactyloditerpenol acetate, a new prenylbisabolane-type diterpene from Aplysia dactylomela with significant in vitro anti-neuroinflammatory activity. Bioorg Med Chem Lett 24:344-8
Li, Jing; Cisar, Justin S; Zhou, Cong-Ying et al. (2013) Simultaneous structure-activity studies and arming of natural products by C-H amination reveal cellular targets of eupalmerin acetate. Nat Chem 5:510-7
Mayer, Alejandro M S; Rodriguez, Abimael D; Taglialatela-Scafati, Orazio et al. (2013) Marine pharmacology in 2009-2011: marine compounds with antibacterial, antidiabetic, antifungal, anti-inflammatory, antiprotozoal, antituberculosis, and antiviral activities; affecting the immune and nervous systems, and other miscellaneous mechanisms of Mar Drugs 11:2510-73
Avilés, Edward; Rodríguez, Abimael D; Vicente, Jan (2013) Two rare-class tricyclic diterpenes with antitubercular activity from the Caribbean sponge Svenzea flava. Application of vibrational circular dichroism spectroscopy for determining absolute configuration. J Org Chem 78:11294-301
Mayer, Alejandro M S; Aviles, Edward; Rodriguez, Abimael D (2012) Marine sponge Hymeniacidon sp. amphilectane metabolites potently inhibit rat brain microglia thromboxane B2 generation. Bioorg Med Chem 20:279-82
Mayer, Alejandro M S; Rodriguez, Abimael D; Berlinck, Roberto G S et al. (2011) Marine pharmacology in 2007-8: Marine compounds with antibacterial, anticoagulant, antifungal, anti-inflammatory, antimalarial, antiprotozoal, antituberculosis, and antiviral activities; affecting the immune and nervous system, and other miscellaneous mec Comp Biochem Physiol C Toxicol Pharmacol 153:191-222
La Clair, James J; Rodriguez, Abimael D (2011) Isolation of the ýý-galactosphingolipid coniferoside using a tumor cell proteome reverse affinity protocol. Bioorg Med Chem 19:6645-53
Crimmins, Michael T; Mans, Mark C; Rodriguez, Abimael D (2010) Total synthesis of the proposed structure of briarellin J. Org Lett 12:5028-31
Jimeýýnez-Romero, Carlos; Ortiz, Idelisse; Vicente, Jan et al. (2010) Bioactive Cycloperoxides Isolated from the Puerto Rican Sponge Plakortis halichondrioides. J Nat Prod :
Avilés, Edward; Rodríguez, Abimael D (2010) Monamphilectine A, a potent antimalarial ?-lactam from marine sponge Hymeniacidon sp: isolation, structure, semisynthesis, and bioactivity. Org Lett 12:5290-3

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