Chemistry Graduate and Undergraduate Program
-Lipid Chemistry and Marine Natural Products: Isolation and Synthesis of New Fatty
Acids of Marine Origin
-New Antiplasmodial and Antifungal Lipids
Our laboratory deals with the structural elucidation, total synthesis and biological activity of novel lipids from marine organisms. Particular emphasis is placed on those lipids with antifungal, antimalarial and cytotoxic properties. Most of the novel marine lipids have been isolated from Caribbean sponges, in particular from symbiotic microorganisms associated with sponges. At present we are working in the synthesis of a series of novel marine fatty acids that have shown important inhibition against the enoyl-ACP-reductase (FabI) enzyme of the protozoan parasite Plasmodium falciparum, the most important agent causing malaria. We are interested in establishing a structure activity relationship with these compounds aimed at discovering the most potent fatty acid against both this parasite and the FabI enzyme. Specifically, we wish to answer questions such as what structural characteristics of these fatty acids favor their Fabl inhibitory activity and how do the Fabl inhibitory activity correlates with changes in carbon chain-length. A student involved in this project will work in the synthesis of several of these fatty acid analogues, gain valuable experience in organic synthesis, and at the same time he will get exposure to experimental techniques in lipidology. At the same time the student will also get experience in marine natural products as new lipids from marine organisms are constantly being isolated in our laboratory.
This model shows the 2-hexadecynoic acid inside the Pf FabG enzyme so as to explain its inhibitory effect. The compounds blue are other isomeric hexadecynoic acids which are not active towards the enzymein. Photo courtesy of Dr. Mire Zloh, School of Pharmacy, University of London.
D. J. Sanabria-Ríos, Y. Rivera-Torres, G. Maldonado-Domínguez, I. Domínguez, C. Ríos, D. Díaz, J. W. Rodríguez, J. S. Altieri-Rivera, E. Ríos-Olivares, G. Cintrón, N. Montano, and N. M. Carballeira “Antibacterial Activity of 2-Alkynoic Fatty Acids Against Multidrug Resistant Bacteria”,Chem. Phys. Lipids, 178, 84-91 (2014).
D. Oyola-Robles, C. Rullán Lind, N. M. Carballeira, and A. Baerga Ortiz “Expression of Dehydratase Domains from a Polyunsaturated Fatty Acid Synthase Increases the Production of Fatty Acids in Escherichia coli”, Enzyme Microb. Tech., 55, 133-139 (2014).
I. J. Santos-Soto, N. Chorna, N. M. Carballeira, J. G. Vélez-Bartolomei, A. T. Méndez, A. Chornyy, and S. Peña de Ortiz “Voluntary Running in Young Adult Mice Reduces Anxiety-Like Behavior and Increases the Accumulation of Bioactive Lipids in the Cerebral Cortex”, PLoS One,8(12): e81459 (2013).
N. M. Carballeira, N. Montano, R. Álvarez-Velilla, C. F. Prada, R. M. Reguera, and R. Balaña-Fouce “Synthesis of Marine a-Methoxylated Fatty Acid Analogs that Effectively Inhibit the Topoisomerase IB from Leishmania donovani with a Mechanism Different from that of Camptothecin”,Mar. Drugs, 11, 3661-3675 (2013).
N. E. Chorna, I. J. Santos-Soto, N. M. Carballeira, J. L. Morales, J. de la Nuez, A. Cátala-Valentín, A. P. Chornyy, A. Vázquez-Montes, and S. Peña de Ortiz “Fatty Acid Synthase as a Factor Required for Exercise-Induced Cognitive Enhacement and Dentate Gyrus Cellular Proliferation”,PLoS One, 8(11): e77845 (2013).
N. M. Carballeira “Recent Developments in the Antiprotozoal and Anticancer Activities of the 2-Alkynoic Fatty Acids”, Chem. Phys. Lipids, 172-173, 58-66 (2013).
D. Oyola-Robles, D. C. Gay, U. Trujillo, J. M. Sánchez-Parés, M. L. Bermúdez, M. Rivera-Díaz, N. M. Carballeira, and A. Baerga-Ortiz “Identification of Novel Protein Domains Required for the Expression of an Active Dehydratase Fragment from a Polyunsaturated Fatty Acid Synthase”, Protein Sci., 22, 954-963 (2013).
E. A. Orellano, M. M. Cartagena, K. Rosado, and N. M. Carballeira “Synthesis of the Novel (±)-2-Methoxy-6-icosynoic Acid – a Fatty Acid that Induces Death of Neuroblastoma Cells”, Chem. Phys. Lipids, 172-173, 14-19 (2013). (this publication was featured in the Global Medical Discovery Series)
N. M. Carballeira, M. Cartagena, D. Sanabria, D. Tasdemir, C. F. Prada, R. M. Reguera, and R. Balaña-Fouce “2-Alkynoic Fatty Acids Inhibit Topoisomerase IB from Leishmania donovani”, Bioorg. Med. Chem. Lett., 22, 6185-6189 (2012).
N. M. Carballeira, M. Cartagena, F. Liu, Z. Chen, C. F. Prada, E. Calvo-Alvarez. R. M. Reguera, and R. Balaña-Fouce “First Total Synthesis of the (±)-2-Methoxy-6-heptadecynoic Acid and Related 2-Methoxylated Analogs as Effective Inhibitors of the Leishmania Topoisomerase IB Enzyme”, Pure Appl. Chem., 84, 1867-1876 (2012).
N. M. Carballeira, R. O’Neill, and D. Silva “First Total Synthesis of (5Z,9Z)-(±)-2-Methoxy-5,9-octadecadienoic Acid, a Marine Derived Methoxylated Analog of Taxoleic Acid”, Chem. Phys. Lipids, in press (2008).
N. M. Carballeira, M. Cartagena, and D. Tasdemir “Fatty Acid Composition of Turkish Rhododendron Species”, J. Am. Oil Chem. Soc., 85, 605-611 (2008).
J. M. de Goeij, L. Moodley, M. Houtekamer, N. M. Carballeira, and F. C. van Duyl “Tracing 13C-enriched Dissolved and Particulate Organic Carbon in the Bacteria-Containing Coral Reef Sponge Halisarca caerulea: Evidence for DOM Feeding”, Limnol. Oceanogr., 53, 1376-1386 (2008).
N. M. Carballeira “New Advances in Fatty Acids as Antimalarial, Antimycobacterial, and Antifungal Agents”, Prog. Lipid Res., 47, 50-61 (2008).
N. M. Carballeira, D. Oyola, J. Vicente, and A. D. Rodríguez “Identification of Novel α-Methoxylated Phospholipid Fatty Acids in the Caribbean Sponge Erylus goffrilleri”, Lipids, 42, 1047-1053 (2007).
D. Tasdemir, B. Topaloglu, R. Perozzo, R. Brun, R. O’Neill, N. M. Carballeira, X. Zhang, P. J. Tonge, A. Linden, and P. Rüedi “Marine Natural Products from the Turkish Sponge Agelas oroides that Inhibit the Enoyl Reductases from Plasmodium falciparum, Mycobacterium tuberculosis and Escherichia coli”, Bioorg. Med. Chem., 15, 6834-6845 (2007).
N. M. Carballeira, R. O’Neill, and K. Parang “Synthesis and Antifungal Properties of a-Methoxy and a-Hydroxyl Substituted 4-Thiatetradecanoic Acids”, Chem. Phys. Lipids, 150, 82-88 (2007).
N. M. Carballeira, N. Montano, J. Vicente, and A. D. Rodríguez “Novel Cyclopropane Fatty Acids from the Phospholipids of the Caribbean Sponge Pseudospongosorites suberitoides”, Lipids, 42, 519-524 (2007).
N. M. Carballeira, D. Sanabria, and D. J. Oyola “An Improved Synthesis for the (Z)-14-Methyl-9-pentadecenoic Acid and its Topoisomerase I Inhibitory Activity”, Arkivoc-Archive for Organic Chemistry, (viii), 49-57 (2007).
N. M. Carballeira, N. Montano, and L. F. Padilla “First Total Synthesis of (Z)-15-Methyl-10-hexadecenoic Acid and the (Z)-13-Methyl-8-tetradecenoic Acid”, Chem. Phys. Lipids, 145, 37-44 (2007).