Publications

Several arenaviruses cause hemorrhagic fever (HF) disease in humans and represent important public health problems in their endemic regions. In addition, evidence indicates that the worldwide-distributed prototypic arenavirus lymphocytic choriomeningitis virus is a neglected human pathogen of clinical significance. There are no licensed arenavirus vaccines, and current antiarenavirus therapy is limited to an off-label use of ribavirin that is only partially effective. Therefore, there is an unmet need for novel therapeutics to combat human pathogenic arenaviruses, a task that will be facilitated by the identification of compounds with antiarenaviral activity that could serve as probes to identify arenavirus-host interactions suitable for targeting, as well as lead compounds to develop future antiarenaviral drugs. Screening of a combinatorial library of Krönhke pyridines identified compound KP-146 [(5-(5-(2,3-dihydrobenzo[b][1,4] dioxin-6-yl)-4′-methoxy-[1,1′-biphenyl]-3-yl)thiophene-2-carboxamide] as having strong anti-lymphocytic choriomeningitis virus (LCMV) activity in cultured cells. KP-146 did not inhibit LCMV cell entry but rather interfered with the activity of the LCMV ribonucleoprotein (vRNP) responsible for directing virus RNA replication and gene transcription, as well as with the budding process mediated by the LCMV matrix Z protein. LCMV variants with increased resistance to KP-146 did not emerge after serial passages in the presence of KP-146. Our findings support the consideration of Kröhnke pyridine scaffold as a valuable source to identify compounds that could serve as tools to dissect arenavirus-host interactions, as well as lead candidate structures to develop antiarenaviral drugs.

Two new chloro-furanocembranolides (1, 2) and two new 1,4-diketo cembranolides (3, 4) were isolated from the crude extract of Leptogorgia sp. together with a new seco-furanocembranolide (5) and the known Z-deoxypukalide (6), rubifolide (7), scabrolide D (8) and epoxylophodione (9). Their structures were determined based on spectroscopic evidence. Four compounds: 1, 2, 7 and 8 were found to activate the proliferation of pancreatic insulin-producing (beta) cells.

Transition metal-free radical arylation of heteroarenes is achieved at room temperature by simply adding aqueous sodium carbonate to a solution of the corresponding heteroarene and arenediazonium salt, which can even be formed in situ. Such an easy, inexpensive and mild methodology has been optimized and applied to the expeditious modification of interesting molecular cores like naphthylimide or bisthienylcyclopentenes.

Host-defense peptides, also called antimicrobial peptides (AMPs), whose protective action has been used by animals for millions of years, fulfill many requirements of the pharmaceutical industry, such as: (1) broad spectrum of activity; (2) unlike classic antibiotics, they induce very little resistance; (3) they act synergically with conventional antibiotics; (4) they neutralize endotoxins and are active in animal models. However, it is considered that many natural peptides are not suitable for drug development due to stability and biodisponibility problems, or high production costs. This review describes the efforts to overcome these problems and develop new antimicrobial drugs from these peptides or inspired by them. The discovery process of natural AMPs is discussed, as well as the development of synthetic analogs with improved pharmacological properties. The production of these compounds at acceptable costs, using different chemical and biotechnological methods, is also commented. Once these challenges are overcome, a new generation of versatile, potent and long-lasting antimicrobial drugs is expected.

Cuban Cultural Heritage explores the role that cultural heritage and museums played in the construction of a national identity in postcolonial Cuba. Starting with independence from Spain in 1898 and moving through Cuban-American rapprochement in 2014, Pablo Alonso González illustrates how political and ideological shifts have influenced ideas about heritage and how, in turn, heritage has been used by different social actors to reiterate their status, spread new ideologies, and consolidate political regimes.

Unveiling the connections between heritage, power, and ideology, Alonso Gonzalez delves into the intricacies of Cuban history, covering key issues such as Cuba's cultural and political relationships with Spain, the United States, the Soviet Union, and so-called Third World countries; the complexities of Cuba's status as a postcolonial state; and the potential future paths of the Revolution in the years to come. This volume offers a detailed look at the function and place of cultural heritage under socialist states.

Our site-selective modification of serine or threonine units in peptides allows the generation of β-substituted dehydroamino acids, which increase peptide resistance to hydrolysis and may improve their biological properties. Both the terminal and internal positions can be modified, and different customizable units can be activated separately. Remarkably, high Z selectivity is achieved, even at internal positions. The conversion involves a one-pot oxidative radical scission/phosphorylation process by using the low-toxicity (diacetoxyiodo)benzene/iodine system as the scission reagent. The resulting α-amino phosphonates undergo a Horner-Wadsworth-Emmons reaction to produce the dehydroamino acid derivatives (in a Z/E ratio of usually >98:2) under mild and metal-free conditions.

Life on oceanic islands deviate in many ways from that on the mainland. Their biodiversity is relatively poor and some groups are well-represented, others not, especially not insects. A scarcity of insects forces birds to explore alternative food, such as nectar and fruit. In this way, island birds may pollinate and disperse seed to an extent unseen on any mainland; they may even first consume floral resources of a plant species and then later harvest the fruit of the same species. Through this biotic reuse, they may act as double mutualists. The latter have never been studied at the level of the network, because they are traditionally considered rare. We sampled pollination and seed-dispersal interactions on Galápagos and constructed a plant-bird mutualism network of 108 plant (12% being double mutualists) and 21 bird species (48% being double mutualists), and their 479 interactions, being either single (95%) or double mutualisms (5%). Double mutualists constitute the core in the pollination-dispersal network, coupling the two link types together. They may also initiate positive feedbacks (more pollination leading to more dispersal), which theoretically are known to be unstable. Thus, double mutualisms may be a necessary, but risky prerequisite to the survival of island biodiversity.

Biomonitoring underpins the environmental assessment of freshwater ecosystems and guides management and conservation. Current methodology for surveys of (macro)invertebrates uses coarse taxonomic identification where species-level resolution is difficult to obtain. Next-generation sequencing of entire assemblages (metabarcoding) provides a new approach for species detection, but requires further validation. We used metabarcoding of invertebrate assemblages with two fragments of the cox1 “barcode” and partial nuclear ribosomal (SSU) genes, to assess the effects of a pesticide spill in the River Kennet (southern England). Operational taxonomic unit (OTU) recovery was tested under 72 parameters (read denoising, filtering, pair merging and clustering). Similar taxonomic profiles were obtained under a broad range of parameters. The SSU marker recovered Platyhelminthes and Nematoda, missed by cox1, while Rotifera were only amplified with cox1. A reference set was created from all available barcode entries for Arthropoda in the BOLD database and clustered into OTUs. The River Kennet metabarcoding produced matches to 207 of these reference OTUs, five times the number of species recognized with morphological monitoring. The increase was due to the following: greater taxonomic resolution (e.g., splitting a single morphotaxon “Chironomidae” into 55 named OTUs); splitting of Linnaean binomials into multiple molecular OTUs; and the use of a filtration-flotation protocol for extraction of minute specimens (meiofauna). Community analyses revealed strong differences between “impacted” vs. “control” samples, detectable with each gene marker, for each major taxonomic group, and for meio- and macrofaunal samples separately. Thus, highly resolved taxonomic data can be extracted at a fraction of the time and cost of traditional nonmolecular methods, opening new avenues for freshwater invertebrate biodiversity monitoring and molecular ecology.

Self-assembled supramolecular gels have recently emerged as promising confined media for the incorporation of a wide range of donor–acceptor chromophoric assemblies, allowing highly efficient photon upconversion processes at weak solar irradiance even under aerobic conditions in some cases. Supramolecular gels made of dense intermo-lecular interaction networks such as hydrogen bonding have been demonstrated to offer effective protection to the excited species against oxygen quenching. This supramolecular approach is reminiscent to biological photon-harvesting systems and constitutes a new paradigm in photon upconversion research. This minireview summarizes the advances in this approach since its first report a few years ago. The possibility of carrying out photon upconversion in supramolecular gel matrices under aerobic conditions has also enabled to combine this process with a single electron transfer in order to carry out challenged chemical reactions such as the photoreduction of aryl halides in air using visible light. The main aspects of this combined strategy and future perspectives are also discussed.

A one-pot efficient, practical and eco-friendly synthesis of tocopherol analogues has been developed using water or solvent free conditions via Passerini and Ugi multicomponent reactions. These reactions can be optimized using microwave irradiation or ultrasound as the energy source. Accordingly, a small library of 30 compounds was prepared for biological tests. The evaluation of the antiproliferative activity in the human solid tumor cell lines A549 (lung), HBL-100 (breast), HeLa (cervix), SW1573 (lung), T-47D (breast), and WiDr (colon) provided lead compounds with GI values between 1 and 5 μM. A structure–activity relationship is also discussed. One of the studied compounds comes up as a future candidate for the development of potent tocopherol-mimetic therapeutic agents for cancer.