Synthesis of 2-Methoxylated Eicosenoic Acids as Potential Inhibitors of L. Donovani TopIB

Sunday, 15 February 2015
Exhibit Hall (San Jose Convention Center)
Nashbly Montano, University of Puerto Rico, Rio Piedras Campus, San Juan, PR
2-Methoxylated acetylenic fatty acids are rare in nature and have mainly been identified in marine organisms. The biological properties of these fatty acids are not well known, but our group have demonstrated that the combination of 2-methoxylation and unsaturation in the fatty acid enhances their potency against protozoal and bacterial organisms and even some against cancer cell lines [1]. The novel diunsaturated (±)-(5Z,9Z)-2-methoxy-5,9-eicosadienoic acid, identified in the Caribbean sponge Erylus goffrilleri, and the (±)-2-methoxy-5,9-eicosadiynoic acid, inhibit the Leishmania donovani TopIB at concentrations of 31 and 22 µM, respectively [2]. To understand the contribution of each unsaturation in (±)-(5Z,9Z)-2-methoxy-5,9-eicosadienoic acid on the inhibition of LdTopIB, we synthesized the (±)-Z-2-methoxy-5-eicosenoic acid and the (±)-Z-2-methoxy-9-eicosenoic acid, and their corresponding acetylenic analogs. The synthesis and comparison of the LdTopIBinhibitory activities between these novel acids and the (±)-(5Z,9Z)-2-methoxy-5,9-eicosadienoic acid will be presented. This work was supported by NIH-RISE (2R25GM061151-13). 1.  Carballeria, N. M., Cartagena, M. M., Li, F., Chen, Z., Prada, C. F., Calvo-Álvarez, E., Reguera, R., Balaña-Fouce, R. Pure Appl. Chem. 2012, 84, 1867-1875; Orellano, E. A., Cartagena, M. M., Rosado, K., Carballeira, N. M. Chem. Phys. Lipids 2013 172-173, 14-19. 2.  Carballeira, N. M., Montano, N., Álvarez-Velilla, R., Prada, C. F., Reguera, R. M., Balaña-Fouce, R. Mar. Drugs 2013, 11, 3661-3675.