Iridium-and Palladium-Based Catalysts in the Pharmaceutical Industry

Transition metal catalysts play a vital role in a wide range of industrial organic processes. The large-scale production of chemicals relying on catalyzed organic reactions represents a sustainable approach to supply society with end products for many daily life applications. Homogeneous (mainly for academic uses) and heterogeneous (crucial in industrial processes) metal-based catalysts have been developed for a plethora of organic reactions. The search for more sustainable strategies has led to the development of a countless number of metal-supported catalysts, nanosystems, and electrochemical and photochemical catalysts. In this work, although a vast number of transition metals can be used in this context, special attention is devoted to Ir-and Pd-based catalysts in the industrial manufacture of pharmaceutical drugs. Pd is by far the most widely used and versatile catalyst not only in academia but also in industry. Moreover, Ir-based complexes have emerged as attractive catalysts, particularly in asymmetric hydrogenation reactions. Ir-and Pd-based asymmetric reductions, aminations, cross-coupling reactions, and C–H activation are covered herein in the production of biologically active compounds or precursors; adaptation to bulk conditions is particularly highlighted.Gobierno de Canarias SD-19/02Ministerio de Ciencia e Innovación PID2020-116460RB-I00, 10.13039/50110001103

Generation of artificial neural networks models in anticancer study

Artificial neural networks (ANNs) have several applications; one of them is the prediction of biological activity. Here, ANNs were applied to a set of 32 compounds with anticancer activity assayed experimentally against two cancer cell lines (A2780 and T-47D). Using training and test sets, the obtained correlation coefficients between experimental and calculated values of activity, for A2780, were 0.804 and 0.829, respectively, and for T-47D, we got 0.820 for the training set and 0.927 for the test set. Com paring multiple linear regression and ANN models, the latter were better suited in establishing relationships between compounds’ structure and their anticancer activity.info:eu-repo/semantics/publishedVersio

Contributions to the radiogenic isotopic fingerprint of Tenerife wine from land, sea and air

We present preliminary results of a study to characterise the radiogenic isotopic fingerprint of wines across the island of Tenerife, Canary Islands, Spain, focussing initially upon Sr. The isotopically juvenile nature of Tenerife rocks supports a hypothesis that all biological material grown on Tenerife should be distinct from most other regions on Earth in terms of Sr isotopes, and especially so from the radiogenic Iberian Peninsula. Pilot data largely support this view, yet we also observe clear evidence for an isotopically evolved component in Tenerife wines. In this contribution, we consider that the unique geography of the Canary Islands may help rationalise these observations. The Canaries are adjacent to the most important atmospheric dust source on Earth, the Saharan Desert, which is largely composed of radiogenic sources of Sr. Along with contributions to the Tenerife terroir from atmospheric dust, we also consider the role that sea spray during storm events may play. Should natural processes fail to explain the patterns we observe, anthropogenic mixing during wine-making using components sourced outside the archipelago is a possibility that must be considered, which has implications for consumer confidence and, by extension, the economy of Tenerife.publishe

One-pot multicomponent green Hantzsch synthesis of 1,2-dihydropyridine derivatives with antiproliferative activity

A rapid route for obtaining unsymmetrical 1,2-dihydropyridines (1,2-DHPs) as opposed to 1,4-dihydropyridines (1,4-DHPs) has been achieved via a one-pot multicomponent Hantzsch reaction. A benign protocol has been developed for the preparation of various 1,2-dihydropyridine derivatives using heterogenized phosphotungstic acid on alumina support (40 wt %). High yields of over 75% have been accomplished in just 2–3.5 h after screening several heterogeneous catalysts and investigating the optimal reaction conditions. The catalyst chosen has passed the heterogeneity test and was shown to have the potential of being reused for up to 8 consecutive cycles before having a significant loss in activity. In addition, aromatic aldehydes gave the aforementioned regioisomer while the classical 1,4-DHPs were obtained when carrying out the reaction using aliphatic aldehydes. The preliminary study of the antiproliferative activity against human solid tumor cells demonstrated that 1,2-DHPs could inhibit cancer cell growth in the low micromolar range.peer-reviewe

Chemoselective Preparation of New Families of Phenolic-Organoselenium Hybrids—A Biological Assessment

Being aware of the enormous biological potential of organoselenium and polyphenolic compounds, we have accomplished the preparation of novel hybrids, combining both pharma-cophores in order to obtain new antioxidant and antiproliferative agents. Three different families have been accessed in a straightforward and chemoselective fashion: carbohydrate-containing N-acylisoselenoureas, N-arylisoselenocarbamates and N-arylselenocarbamates. The nature of the organoselenium framework, number and position of phenolic hydroxyl groups and substituents on the aromatic scaffolds afforded valuable structure–activity relationships for the biological as-says accomplished: antioxidant properties (antiradical activity, DNA-protective effects, Glutathione peroxidase (GPx) mimicry) and antiproliferative activity. Regarding the antioxidant activity, selenocar-bamates 24–27 behaved as excellent mimetics of GPx in the substoichiometric elimination of H2O2 as a Reactive Oxygen Species (ROS) model. Isoselenocarbamates and particularly their selenocarbamate isomers exhibited potent antiproliferative activity against non-small lung cell lines (A549, SW1573) in the low micromolar range, with similar potency to that shown by the chemotherapeutic agent cisplatin (cis-diaminodichloroplatin, CDDP) and occasionally with more potency than etoposide (VP-16).Ministerio de Ciencia e Innovación PID2020-116460RB-I00Junta de Andalucía FQM134Gobierno de las Islas Canarias ProID202001010

Molecular Simplification in Bioactive Molecules: Formal Synthesis of (+)-Muconin

7 páginas, 1 figura, 7 esquemas, 1 tabla.-- El PDF es la versión post-print.The concept of molecular simplification as a drug design strategy to shorten synthetic routes, while keeping or enhancing the biological activity of the lead drug, has been applied to (+)-muconin, an acetogenin with remarkable cytotoxicity. A novel approach that enables the stereoselective synthesis of such a natural compound or its enantiomer from a common precursor is described. An additional advantage of the method is complete stereochemical control and the decrease in the number of chemical steps required, thus providing an enhancement of the overall yield. Antiproliferative studies against the human solid tumor cell lines showed that the aliphatic chain-THF/THP fragment of (+)-muconin has modest cytotoxic activity. The strategy opens the way to preparing novel bioactive acetogenin analogues by shorter synthetic routes.The authors thank the MYCT (PPQ2002- 04361-C04-02) of Spain and the Canary Islands Government for supporting this research. F.R.P.C. thanks CajaCanarias for a FPI fellowship. R.C. thanks the Spanish MEC for a FPU fellowship. J.M.P. thanks ICIC for a postdoctoral fellowship.Peer reviewe

Acanthamoeba castellanii: a new high-throughput method for drug screening in vitro

Despite significant public health impact, there is no specific antiprotozoal therapy for prevention and treatment of Acanthamoeba castellanii infection. There is a need for new and efficient anti-Acanthamoeba drugs that are less toxic and can reduce treatment duration and frequency of administration. In this context a new, rapid and sensitive assay is required for high-throughput activity testing and screening of new therapeutic compounds. A colorimetric assay based on sulforhodamine B (SRB) staining has been developed for anti-Acanthamoeba drug susceptibility testing and adapted to a 96-well microtiter plate format. Under these conditions chlorhexidine was tested to validate the assay using two clinical strains of A. castellanii (Neff strain, T4 genotype [IC50 4.68±0.6 _M] and T3 genotype [IC50 5.69±0.9 _M]). These results were in good agreement with those obtained by the conventional Alamar Blue assay, OCR cytotoxicity assay and manual cell counting method. Our new assay offers an inexpensive and reliable method, which complements current assays by enhancing high-throughput anti-Acanthamoeba drug screening capabilities

Mechanochemical Synthesis of Nickel-Modified Metal–Organic Frameworks for Reduction Reactions

In this work, we report the incorporation of nickel oxide nanoparticles into a metal–organic framework (MOF) structure by a solvent-free mechanochemical strategy. In particular, the zirconium-based MOF UiO-66 was modified with different Ni loadings and characterized using complementary techniques including X-ray diffraction (XRD), N2 porosimetry and X-ray photoelectron spectroscopy (XPS). The catalytic potential of the as-prepared Ni/UiO-66 materials in the hydrogenation reaction of methyl levulinate using 2-propanol as hydrogen donor solvent has been investigated under flow conditions. Under optimized conditions, the 5%Ni/UiO-66 led to the best catalytic performance (70% yield, 100% selectivity to gamma-valerolactone), which could be attributed to the higher content of the Ni species within the MOF structure. The obtained results are promising and contribute to highlighting the great potential of MOFs in biomass upgrading processes, opening the path to the sustainable development of the chemical industry

A small molecule tubulin depolymerizing agent identified by a phenotypic drug discovery approach

In the scenario of drug discovery, numerous in vitro testing initiatives had been established. Thus far, no general methodology is reputable and literature on this hot topic is scarce. In this respect, we propose a strategy based on a Phenotypic Drug Discovery approach. Within our program directed at the discovery of new antitumor agents, we have focused our attention on compounds that disturb the cell cycle. Our strategy relies on the use of a set of biological assays organized in a modular fashion. Herein, we exemplified this strategy with a family of propargylic enol ether derivatives. Using different assays in sequential stages and in a stepwise manner, our studies allowed us to understand the bioactivity of this family of compounds and led us to identify tubulin as the main molecular target.info:eu-repo/semantics/publishedVersio