3D molecular structure determination is a challenge for organic compounds or natural products available in minute amounts. Proton/proton and proton/carbon correlations yield the constitution. J couplings and NOEs oftentimes supported by one-bond 1H,13C residual dipolar couplings (RDCs) or by 13C residual chemical shift anisotropies (RCSAs) provide the relative configuration. However, these RDCs or carbon RCSAs rely on 1% natural abundance of 13C preventing their use for compounds available only in quantities of a few 10’s of µgs. By contrast, 1H RCSAs provide similar information on spatial orientation of structural moieties within a molecule, while using the abundant 1H spin. Herein, 1H RCSAs are accurately measured using constrained aligning gels or liquid crystals and applied to the 3D structural determination of molecules with varying complexities. Even more, deuterated alignment media allow the elucidation of the relative configuration of around 35 µg of a briarane compound isolated from Briareum asbestinum.

The pyrrole-imidazoles, a group of alkaloids commonly found in marine sponges belonging to the genus Agelas, display a wide range of biological activities. Herein, we report the first chemical study of the secondary metabolites of the sponge A. dilatata from the coastal area of the Yucatan Peninsula (Mexico). In this study, we isolated eight known alkaloids from an organic extract of the sponge. We used NMR and MS analysis and comparison with existing databases to characterize the alkaloids: ageliferin (1), bromoageliferin (2), dibromoageliferin (3), sceptrin (4), nakamuric acid (5), 4-bromo-1H-pyrrole-2-carboxylic acid (6), 4,5-dibromopyrrole-2-carboxylic acid (7) and 3,7-dimethylisoguanine (8). We also evaluated, for the first time, the activity of these alkaloids against the most problematic multidrug-resistant (MDR) pathogens, i.e., the Gram-negative bacteria Pseudomonas aeruginosa, Klebsiella pneumoniae and Acinetobacter baumannii. Bromoageliferin (2) displayed significant activity against P. aeruginosa. Comparison of the antibacterial activity of ageliferins 1–3 (of similar structure) against P. aeruginosa revealed some relationship between structure and activity. Furthermore, in in vitro assays, 2 inhibited growth and biofilm production in clinical strains of P. aeruginosa. Moreover, 2 increased the survival time in an in vivo Galleria mellonella model of infection. The findings confirm bromoageliferin (2) as a potential lead for designing new antibacterial drugs.

Dermacoccus abyssi strain MT1.1T is a piezotolerant actinobacterium that was isolated from Mariana Trench sediment collected at a depth of 10898 m. The organism was found to produce ten dermacozines (A‒J) that belonged to a new phenazine family and which displayed various biological activities such as radical scavenging and cytotoxicity. Here, we report on the isolation and identification of a new dermacozine compound, dermacozine M, the chemical structure of which was determined using 1D and 2D-NMR, and high resolution MS. A whole genome sequence of the strain contained six secondary metabolite-biosynthetic gene clusters (BGCs), including one responsible for the biosynthesis of a family of phenazine compounds. A pathway leading to the biosynthesis of dermacozines is proposed. Bioinformatic analyses of key stress-related genes provide an insight into how the organism adapted to the environmental conditions that prevail in the deep-sea.

Two new spongian furanoditerpenes, 3β-hydroxyspongia-13(16),14-dien-2-one (1) and 19-dehydroxy-spongian diterpene 17 (2), along with five known terpenes, the spongian furanoditerpenes 9-nor-3-hydroxyspongia-3,13(16),14-trien-2-one (3), 3β,19 dihydroxyspongia-13(16),14-dien-2-one (epispongiadiol) (4) and spongian diterpene 17 (5), the furanoditerpene ambliol C (6), and the sesterterpene scalarin (7), were isolated from the methanolic extract of the sponge Spongia tubulifera, collected in the Mexican Caribbean. The planar structures of the new compounds were elucidated by 1D/2D NMR and IR spectroscopic analysis, high resolution electrospray mass spectrometry (HRESIMS), and comparison of their spectral data with those reported in the literature. Absolute configurations were determined by comparison of the experimental electronic circular dichroism (ECD) spectrum with those calculated by time-dependent density functional theory (TDDFT). Compounds 1, 4, and 6 displayed weak cytotoxic activity against different human tumour cell lines.

Mexico is one of the three areas of the world with the greatest terrestrial and cultural biological diversity. The diversity of Mexican medicinal flora has been studied for a long time and several bioactive compounds have been isolated. The investigation of marine resources, and particularly the potential of Mexican marine resources, has not been intensively investigated, even though the Yucatan Peninsula occupies 17.4% of the total of the Mexican coast, with great biological diversity in its coasts and the ocean. There are very few studies on the chemistry of natural products from marine organisms that were collected along the coasts of the Yucatan Peninsula and most of them are limited to the evaluation of the biological activity of their organic extracts. The investigations carried out on marine species from the Yucatan Peninsula resulted in the identification of a wide structural variety of natural products that include polyketides, terpenoids, nitrogen compounds, and biopolymers with cytotoxic, antibacterial, antifouling, and neurotoxic activities. This review describes the literature of bioprospecting and the exploration of the natural product diversity of marine organisms from the coasts of the Yucatan Peninsula up to mid-2019.

Ruthenium(II) complexes are currently considered attractive alternatives to the widely used platinum-based drugs. We present herein the synthesis and characterization of half-sandwich ruthenium compounds formulated as [Ru(p-cymene)(L)Cl]-[CF 3 SO 3 ] (L = 1,1-bis(methylenediphenylphosphano)ethylene, 1; L = 1,1-bis(diphenylphosphano)ethylene, 2), which were characterized by elemental analysis, mass spectrometry, 1 H and 31 P{ 1 H} NMR, UV−vis and IR spectroscopy, conductivity measurements and cyclic voltammetry. The molecular structures for both complexes were determined by single-crystal X-ray diffraction. Their cytotoxic activity was evaluated using the MTT assay against human tumor cells, namely ovarian (A2780) and breast (MCF7 and MDA-MB-231). Both complexes were active against breast adenocarcinoma cells, with complex 1 exhibiting a quite remarkable cytotoxicity in the submicromolar range. Interestingly, at concentrations equivalent to the IC 50 values in the MCF7 cancer cells, complexes 1 and 2 presented lower cytotoxicity in normal human primary fibroblasts. The antiproliferative effects of 1 and 2 in MCF7 cells might be associated with the induction of reactive oxygen species (ROS), leading to a combined cell death mechanism via apoptosis and autophagy. Despite the fact that in vitro a partial intercalation between complexes and DNA was observed, no MCF7 cell cycle delay or arrest was observed, indicating that DNA might not be a direct target. Complexes 1 and 2 both exhibited a moderate to strong interaction with human serum albumin, suggesting that protein targets may be involved in their mode of action. Their acute toxicity was evaluated in the zebrafish model. Complex 1 (the most toxic of the two) exhibited a lethal toxicity LC 50 value about 1 order of magnitude higher than any IC 50 concentrations found for the cancer cell models used, highlighting its therapeutic relevance as a drug candidate in cancer chemotherapy.

Octopus maya is a major socio-economic resource from the Yucatán Peninsula in Mexico. In this study we report for the first time the chemical composition of the saliva of O. maya and its effect on natural prey, i.e. the blue crab (Callinectes sapidus), the crown conch snail (Melongena corona bispinosa), as well as conspecifics. Salivary posterior glands were collected from octopus caught by local fishers and extracted with water; this extract paralyzed and predigested crabs when it was injected into the third pereiopod. The water extract was fractionated by membrane ultrafiltration with a molecular weight cut-off of 3kDa leading to a metabolic phase (>3kDa) and a neurotoxic fraction (<3kDa). The neurotoxic fraction injected in the crabs caused paralysis and postural changes. Crabs recovered to their initial condition within two hours, which suggests that the effects of the neurotoxic fraction were reversible. The neurotoxic fraction was also active on O. maya conspecifics, partly paralyzing and sedating them; this suggests that octopus saliva might be used among conspecifics for defense and for reduction of competition. Bioguided separation of the neurotoxic fraction by chromatography led to a paralysis fraction and a relaxing fraction. The paralyzing activity of the saliva was exerted by amino acids, while the relaxing activity was due to the presence of serotonin. Prey-handling studies revealed that O. maya punctures the eye or arthrodial membrane when predating blue crabs and uses the radula to bore through crown conch shells; these differing strategies may help O. maya to reduce the time needed to handle its prey.

Viral infections are one of the main human health problems in recent decades and the cancer remains one of the most lethal diseases worldwide. The development of new antiviral drugs for the treatment of human adenovirus (HAdV) infections continues to be a challenging goal for medicinal chemistry. There is no specific antiviral drug approved to treat infections caused by HAdV so far and the off-label treatments currently available show great variability in their effectiveness. In relation to cancer, most of the available drugs are designed to act on specific targets by altering the activity of involved transporters and genes. Taking into account the high antiviral and antiproliferative activity against tumor cell lines displayed by some marine natural products reported in the literature, sixty five marine organisms were selected: 51 sponges (Porifera), 13 ascidians (Chordata), and 1 gorgonian (Cnidaria), collected from Yucatan Peninsula, Mexico, to evaluate their antiviral activity against human adenovirus type 5 (HAdV5) and their anticancer properties against five human tumor cell lines, namely human lung carcinoma (A549), human skin melanoma (A2058), hepatocyte carcinoma (HepG2), breast adenocarcinoma (MCF7), and pancreas carcinoma (MiaPaca-2). Eleven extracts displayed anti-HAdV activity being the organic extracts of Dysidea sp., Agelas citrina, Chondrilla sp., Spongia tubulifera, and Monanchora arbuscula the five most active ones. On the other hand, 24 extracts showed antiproliferative activity against at least one tumor cell line, being the extracts of the ascidian Eudistoma amanitum and the sponge Haliclona (Rhizoniera) curacaoensis the most active ones. This work constitutes the first wide antiviral and antiproliferative screening report of extracts from the marine sponges, ascidians, and a gorgonian collected from the Yucatan Peninsula, Mexico.