Productos naturales bioactivos de organismos marinos de la Península de Yucatán, México

Abstract

This doctoral thesis describes the first exhaustive research on marine natural products from organisms collected along the coasts of the Yucatan Peninsula, Mexico. A total of 65 organisms were collected that correspond to 55 different species of which 41 are sponges, 13 ascidians and 1 gorgonian. The bioguided isolation strategy and dereplication techniques were used, through which we were able to obtain 31 molecules, of which 10 were found to be new natural compounds, showing some of them interesting biological activities. It should be noted that for the structural determination of some of the new compounds, the application of two new methodologies for the determination of the relative configuration of marine natural products has been used for the first time: the proton chemical shift anisotropy (1H RCSA) and the use of variable temperature and solvent dependent NMR J-based configurational analysis. Chapter 1. A compilation is made of the publications that collect the research in the area of marine natural products of the Yucatan Peninsula until the middle of the year 2019. This bibliographic review gave rise to a publication in the journal Marine Drugs (Mar. Drugs. 2020, 18, 59). Chapter 2. The collection of 65 marine organisms on the coasts of the Yucatan Peninsula, Mexico and their subsequent extraction is described in order to obtain the corresponding organic extracts. The results of the antibacterial, antiviral and antiproliferative activities of all the extracts obtained are presented below. The biodirected fractionation of one of the marine extracts allowed to isolate and identify the compounds that cause antibacterial activity for the Amphimedon compresssa sponge. Chapter 3. The isolation, structural determination and pharmacological evaluation of the pure compounds obtained from sponges Spongia tubulifera, Ircinia felix, Agelas dilatata and gorgonian Briareum asbestinum, organisms collected on the coasts of the Yucatan Peninsula, Mexico, are described. The structural elucidation of the molecules was made from the use of NMR, UV and IR and spectrometric (MS) spectroscopic techniques, while the absolute configuration was obtained from computational calculations (DFT), electronic circular dichroism (ECD) and X-rays. Three of the compounds isolated of S. tubulifera showed a cytotoxic activity against cancer cell lines, two other compounds isolated of I. felix showed a very potent antiviral activity against two types of viruses and finally two of the secondary metabolites isolated of A. dilatata revealed activity against two multiresistant bacterial strains. Chapter 4. The application of two new methodologies for the determination of the relative configuration of two new marine natural products is presented: a) the use of anisotropic proton NMR (1H RCSA) to obtain the relative configuration of the briarane B-3 in scale of micrograms of sample and the application of the variable temperature and solvent dependent NMR J-based configurational analysis to determine the relative configuration of nocardiomycin.