Modulation of the Antimelanoma Activity Imparted to Artemisinin Hybrids by the Monoterpene Counterpart.

Molecular hybridization is a widely used strategy in drug discovery and development processes that consists of the combination of two bioactive compounds toward a novel entity. In the current study, two libraries of hybrid derivatives coming from the linkage of sesquiterpene counterparts dihydroartemisinin and artesunic acid, with a series of monoterpenes, were synthesized and evaluated by cell viability assay on primary and metastatic melanoma cell lines. Almost all the obtained compounds showed micromolar antimelanoma activity and selectivity toward the metastatic form of this cancer.

Serendipitous Identification of Azine Anticancer Agents Using a Privileged Scaffold Morphing Strategy.

The use of privileged scaffolds as a starting point for the construction of libraries of bioactive compounds is a widely used strategy in drug discovery and development. Scaffold decoration, morphing and hopping are additional techniques that enable the modification of the chosen privileged framework and better explore the chemical space around it. In this study, two series of highly functionalized pyrimidine and pyridine derivatives were synthesized using a scaffold morphing approach consisting of triazine compounds obtained previously as antiviral agents.

Synthesis of Benzoxazines by Heterogeneous Multicomponent Biochemo Multienzymes Cascade Reaction.

This work describes the possibility to combine multicomponent chemistry and multienzymes cascade transformations in a unique reactive framework to yield highly functionalized 1,4-benzoxazines under favorable heterogeneous conditions. The synthetic scheme involved the generation in situ of electrophilic reactive quinone intermediates of tyrosol esters catalyzed by lipase M and tyrosinase followed by nucleophilic 1,6-Michael addition of selected α-amino acid methyl esters, and successive intramolecular lactonization and aromatization processes. The immobilization of the multienzymes cascade on electroactive lignin nanoparticles improved the sustainability and recyclability of the overall system.

Molecular Dynamics Investigations of Human DNA-Topoisomerase I Interacting with Novel Dewar Valence Photo-Adducts: Insights into Inhibitory Activity.

Chronic exposure to ultraviolet (UV) radiation is known to induce the formation of DNA photo-adducts, including cyclobutane pyrimidine dimers (CPDs) and Dewar valence derivatives (DVs). While CPDs usually occur at higher frequency than DVs, recent studies have shown that the latter display superior selectivity and significant stability in interaction with the human DNA/topoisomerase 1 complex (TOP1). With the aim to deeply investigate the mechanism of interaction of DVs with TOP1, we report here four all-atom molecular dynamic simulations spanning one microsecond.

Biosynthesis of Novel Ascorbic Acid Esters and Their Encapsulation in Lignin Nanoparticles as Carriers and Stabilizing Systems.

A dual-target strategy was designed for the application of lignin nanoparticles in the lipase mediated biosynthesis of novel 3--ethyl-L-ascorbyl-6-ferulate and 3--ethyl-L-ascorbyl-6-palmitate and in their successive solvent-shift encapsulation in order to improve stability and antioxidant activity against temperature and pH-dependent degradation. The loaded lignin nanoparticles were fully characterized in terms of kinetic release, radical scavenging activity and stability under pH 3 and thermal stress (60 °C), showing improved antioxidant activity and high efficacy in the protection of ascorbic acid esters from degradation.

Synthesis of Artesunic Acid-Coumarin Hybrids as Potential Antimelanoma Agents.

Current therapy against melanoma relies on surgical treatment or, in alternative, on conventional drug therapy. Often these therapeutic agents are ineffective due to the development of resistance phenomena. For this purpose, chemical hybridization emerged as an effective strategy to overcome the development of drug resistance.

Tuning the Effect of Chitosan on the Electrochemical Responsiveness of Lignin Nanoparticles.

Chitosan and lignin mixed nanoparticles were prepared by layer-by-layer and nanoprecipitation methodologies as responsive platforms for sustainable biosensors. The novel nanoparticles showed effective chemophysical and electrochemical properties dependent on the preparation methodology, molecular weight of chitosan, and type of lignin. HOMO-LUMO energy gap calculations suggested the presence of structure-activity relationships between the electrochemical responsiveness and the order and orientation of lignin aromatic subunits and chitosan chains in the nanodevices.

A Green Blue LED-Driven Two-Liquid-Phase One-Pot Procedure for the Synthesis of Estrogen-Related Quinol Prodrugs.

Quinol derivatives of estrogens are effective pro-drugs in steroid replacement therapy. Here, we report that these compounds can be synthesized in one-pot conditions and high yield by blue LED-driven photo-oxygenation of parent estrogens. The oxidation was performed in buffer and eco-certified 2-methyltetrahydrofuran as the two-liquid-phase reaction solvent, and in the presence of meso-tetraphenyl porphyrin as the photosensitizer.

Privileged Scaffold Decoration for the Identification of the First Trisubstituted Triazine with Anti-SARS-CoV-2 Activity.

Current therapy against severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) are based on the use of Remdesivir , Molnupiravir , and the recently identified Nirmatrelvir . Unfortunately, these three drugs showed some limitations regarding potency and possible drug-drug interactions. A series of derivatives coming from a decoration approach of the privileged scaffold s-triazines were synthesized and evaluated against SAR-CoV-2.

First Evidence of Pheomelanin-UVA-Driven Synthesis of Pummerer's Ketones by Peroxidase-Mediated Oxidative Coupling of Substituted Phenols.

Photoexcitation of pheomelanin produces high-energy singlet oxygen and the superoxide anion, which are reactive species in damage of cellular targets. In principle, these species can be involved in processes of synthetic utility when adequate experimental conditions are defined. Here, we describe that pheomelanin performs as a selective UVA antenna for the horseradish peroxidase oxidative coupling of substituted phenols to biologically active Pummerer's ketones under 2-methyltetrahydrofuran/buffer biphasic conditions.

Multicomponent Synthesis of Diaminopurine and Guanine PNA's Analogues Active against Influenza A Virus from Prebiotic Compounds.

Peptide nucleic acids (PNAs) play a key role in prebiotic chemistry as a chimera between RNA and proteins. We developed an alternative synthesis of bioactive PNA's diaminopurine and guanine analogues from prebiotic compounds, such as aminomalononitrile (AMN), urea, and guanidine, using a two-step multicomponent microwave-assisted and solvent-free approach in the presence of selected amino acids. The novel derivatives showed selective inhibitory activity against influenza virus A/Puerto Rico/8/34 H1N1 encompassing the range of nanomolar activity.

Molecular Docking and Dynamics Simulation Revealed the Potential Inhibitory Activity of New Drugs against Human Topoisomerase I Receptor.

Human Topoisomerase I (hTop1p) is a ubiquitous enzyme that relaxes supercoiled DNA through a conserved mechanism involving transient breakage, rotation, and binding. Htop1p is the molecular target of the chemotherapeutic drug camptothecin (CPT). It causes the hTop1p-DNA complex to slow down the binding process and clash with the replicative machinery during the S phase of the cell cycle, forcing cells to activate the apoptotic response.

Lignin Nanoparticles as Sustainable Photoprotective Carriers for Sunscreen Filters.

Sunscreen filters may be degraded after prolonged UV exposure with loss of their shielding property and generation of harmful radical species. They are contained in cosmetic formulations in high concentrations, so the improvement of photostability is of relevance for safety concerns. We report here that lignin nanoparticles are sustainable carriers and photostabilizers of two common UV chemical filters, namely, avobenzone and octyl methoxycinnamate.

A Photochemoenzymatic Hunsdiecker-Borodin-Type Halodecarboxylation of Ferulic Acid.

A photochemoenzymatic halodecarboxylation of ferulic acid was achieved using vanadate-dependent chloroperoxidase as (bio)catalyst and oxygen and organic solvent as sole stoichiometric reagents in a biphasic system. Performance and selectivity were improved through a phase transfer catalyst, reaching a turnover number of 660.000 for the enzyme.

Nanoparticles of Lignins and Saccharides from Fishery Wastes as Sustainable UV-Shielding, Antioxidant, and Antimicrobial Biofillers.

Lignin nanoparticles containing saccharides from fishery wastes were prepared as sustainable biofillers for advanced materials. Organosolv lignin and Kraft lignin were used as polyphenol components in association with chitosan and chitooligosaccharides. The chemophysical and biological activities of lignin/saccharide nanoparticles, such as UV-shielding, antioxidant, and antimicrobial activities, were found to be dependent on both molecular weight and deacetylation degree of saccharides, with the best performance being obtained in the presence of low-molecular-weight and highly deacetylated chitooligosaccharides.

Laccase Mediator Cocktail System as a Sustainable Skin Whitening Agent for Deep Eumelanin Decolorization.

The overproduction of eumelanin leads to a panel of unaesthetic hyper-pigmented skin diseases, including melasma and age spots. The treatment of these diseases often requires the use of tyrosinase inhibitors, which act as skin whitening agents by inhibiting the synthesis of eumelanin, with harmful side effects. We report here that laccase from in association with a cocktail of natural phenol redox mediators efficiently degraded eumelanin from , offering an alternative procedure to traditional whitening agents.

Aminomalononitrile inspired prebiotic chemistry as a novel multicomponent tool for the synthesis of imidazole and purine derivatives with anti-influenza A virus activity.

Amino imidazole carbonitrile derivatives decorated with α-amino acid side-chains have been synthesized by a multicomponent microwave assisted reaction inspired by the prebiotic chemistry of aminomalononitrile as a tool for generating high chemical diversity. These compounds were used as annulation synthons for the preparation of 8,9-disubstituted-6,9-dihydro-1-purin-6-ones by reaction with formic acid as a simple C-1 donor reagent. The novel heterocycles were characterized by significant activity against influenza A virus, amino imidazole carbonitrile derivatives showing the highest activity.

Meteorite-catalyzed intermolecular -glycosylation produces nucleosides under proton beam irradiation.

Di-glycosylated adenines act as glycosyl donors in the intermolecular -glycosylation of pyrimidine nucleobases under proton beam irradiation conditions. Formamide and chondrite meteorite NWA 1465 increased the yield and the selectivity of the reaction. The glycosyl transfer process was highly regioselective in yielding canonical -pyrimidine nucleosides, the natural β-anomers prevailing in the presence of formamide and NWA 1465.

Investigation of fungal biomolecules after Low Earth Orbit exposure: a testbed for the next Moon missions.

The Moon is characterized by extremely harsh conditions due to ultraviolet irradiation, wide temperature extremes, vacuum resulting from the absence of an atmosphere and high ionizing radiation. Therefore, its surface may provide a unique platform to investigate the effects of such conditions. For lunar exploration with the Lunar Gateway platform, exposure experiments in Low Earth Orbit are useful testbeds to prepare for lunar space experiments and to understand how and if potential biomarkers are influenced by extra-terrestrial conditions.

Lignin Nanoparticles Deliver Novel Thymine Biomimetic Photo-Adducts with Antimelanoma Activity.

We report here the synthesis of novel thymine biomimetic photo-adducts bearing an alkane spacer between nucleobases and characterized by antimelanoma activity against two mutated cancer cell lines overexpressing human Topoisomerase 1 (TOP1), namely SKMEL28 and RPMI7951. Among them, Dewar Valence photo-adducts showed a selectivity index higher than the corresponding pyrimidine-(6-4)-pyrimidone and cyclobutane counterpart and were characterized by the highest affinity towards TOP1/DNA complex as evaluated by molecular docking analysis. The antimelanoma activity of novel photo-adducts was retained after loading into UV photo-protective lignin nanoparticles as stabilizing agent and efficient drug delivery system.

The role of borosilicate glass in Miller-Urey experiment.

We have designed a set of experiments to test the role of borosilicate reactor on the yielding of the Miller-Urey type of experiment. Two experiments were performed in borosilicate flasks, two in a Teflon flask and the third couple in a Teflon flask with pieces of borosilicate submerged in the water. The experiments were performed in CH, N, and NH atmosphere either buffered at pH 8.

Fungal Biomarkers Stability in Mars Regolith Analogues after Simulated Space and Mars-like Conditions.

The discovery of life on other planets and moons in our solar system is one of the most important challenges of this era. The second ExoMars mission will look for traces of extant or extinct life on Mars. The instruments on board the rover will be able to reach samples with eventual biomarkers until 2 m of depth under the planet's surface.

Multicomponent Reactions in the Synthesis of Antiviral Compounds.

Background: Multicomponent reactions are one-pot processes for the synthesis of highly functionalized hetero-cyclic and hetero-acyclic compounds, often endowed with biological activity.

Objective: Multicomponent reactions are considered green processes with a high atom economy. In addition, they present advantages compared to the classic synthetic methods, such as high efficiency and low waste production.

Dendrimeric Structures in the Synthesis of Fine Chemicals.

Dendrimers are highly branched structures with a defined shape, dimension, and molecular weight. They consist of three major components: the central core, branches, and terminal groups. In recent years, dendrimers have received great attention in medicinal chemistry, diagnostic field, science of materials, electrochemistry, and catalysis.