Advances in bio/chemical approaches for sustainable recycling and recovery of rare earth elements from secondary resources.

Rare Earth Elements (REEs) are indispensable in the growing smart technologies, such as smart phones and electronic devices, renewable energy, new generation of hybrid cars, etc. These elements are naturally occurring in specific geological deposits (bastnäsite, monazite, and xenotime), primarily concentrated in the regions of China, Australia, and the USA. The extraction and processing of REEs and the mismanagement of secondary REE resources, such as industrial waste, end-of-life materials, and mining by-products, raise major environmental and health concerns. Recycling represents a convincing solution, avoiding the necessity to separate low-value or coexisting radioactive elements when REEs are recovered from raw ore. Despite these advantages, only 1 % of REEs are usually recycled. This review overreached strategies for recycling REEs from secondary resources, emphasizing their pivotal role. The predominant approach for recycling REEs involves hydrometallurgical processing by leaching REEs from their origins using acidic solutions and then separating them from dissolved impurities using techniques like liquid-liquid extraction, membrane separation, chromatography, adsorption, flotation, and electrochemical methods. However, these methods have notable disadvantages, particularly their over requirements for water, reagents, and energy. Biohydrometallurgy introduces an innovative alternative using microorganisms and their metabolites to extract REEs through bioleaching. Other investigations are carried out to recover REEs through biological strategies, including biosorption, affinity chromatography with biological ligands, bioflotation employing biological surfactants, and bioelectrochemical methods. However, biohydrometallurgical processes can also be relatively slow and less suitable for large-scale applications, often lacking specificity for targeted REEs recovery. Overcoming these challenges necessitates ongoing research and development efforts to advance recycling technologies.

A High-throughput Screening of a Chemical Compound Library in Ovarian Cancer Stem Cells.

BACKGROUND: Epithelial ovarian cancer has a poor prognosis, mostly due to its late diagnosis and the development of drug resistance after a first platinum-based regimen. The presence of a specific population of "cancer stem cells" could be responsible of the relapse of the tumor and the development of resistance to therapy. For this reason, it would be important to specifically target this subpopulation of tumor cells in order to increase the response to therapy. METHOD: We screened a chemical compound library assembled during the COST CM1106 action to search for compound classes active in targeting ovarian stem cells. We here report the results of the high-throughput screening assay in two ovarian cancer stem cells and the differentiated cells derived from them. RESULTS AND CONCLUSION: Interestingly, there were compounds active only on stem cells, only on differentiated cells, and compounds active on both cell populations. Even if these data need to be validated in ad hoc dose response cytotoxic experiments, the ongoing analysis of the compound structures will open up to mechanistic drug studies to select compounds able to improve the prognosis of ovarian cancer patients.

Recent advances in drug design of epidermal growth factor receptor inhibitors.

The tyrosine kinase epidermal growth factor receptor (EGFR) has emerged in recent years as a key and validated target of targeted therapies for solid tumors. It plays a central role in oncology since it is involved in many steps of tumor progression such as proliferation, angiogenesis, invasiveness, decreased apoptosis, and loss of differentiation. Recent advances in targeted therapies have demonstrated that tyrosine kinase inhibitors (TKIs), have provided a marked benefit to subsets of patients whose tumors harbor specific genetic abnormalities. However, resistance phenomenon appears rapidly and patients with EGFR mutations acquire resistance to TKI inhibitors decreasing therefore the median time to disease progression to few months. Several strategies were envisioned to overcome this resistance, such as dual-target inhibitors, multitarget and combined therapy. This review summarizes recent advances in TKIs development with special focus on rational strategies for the design of potent EGFR inhibitors including molecular modeling studies based on crystallographic data. Such advances open the way for new research possibilities in modern medicinal chemistry combined to structure-based drug design.

Bicyclic anti-VZV nucleosides: Thieno analogues retain full antiviral activity.

Thieno analogues of the potent and selective furo-pyrimidine anti-VZV nucleoside family are herein reported. The compounds retain full antiviral potency in comparison to the furo parent.

Incorporation of a novel nucleobase allows stable oligonucleotide-directed triple helix formation at the target sequence containing a purine.pyrimidine interruption.

Thermal denaturation experiments have established that an oligonucleotide incorporating the artificial nucleobase S, does form a stable triplex with a double stranded DNA which exhibits a pyrimidine interruption within the oligopurine sequence.

DNA triplex structures are stabilized by the incorporation of 3'-endo blocked pyrimidine nucleosides in the Hoogsteen strand.

A short route to pyrimidine locked nucleosides has been developed for their incorporation in triplex forming oligonucleotides (TFO). Compared to oligonucleotides built with standard nucleosides, the modified TFOs containing 3'-endo blocked residues formed, with their corresponding DNA duplexes, more stable triple helix systems, an effect which might be ascribed to the 3'-endo pucker of the modified nucleoside residues.

Synthesis and anti-HIV activity of novel N-1 side chain-modified analogs of 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine (HEPT).

A series of 33 N-1 side chain-modified analogs of 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine (1, HEPT) were synthesized and evaluated for their anti-HIV-1 activity. In particular, the influence of substitution of the terminal hydroxy group of the acyclic structure of HEPT and the structural rigidity of this side chain were investigated. Halo (7, 8), azido (9), and amino (10-15) derivatives were synthesized from HEPT via the p-tosylate derivative 6. Acylation of the primary amine 15 afforded the amido analogs 16-20. The diaryl derivatives 26-29 were prepared by reaction of HEPT, or of the 6-(2-pyridylthio) analog 23, with diaryl disulfides in the presence of tri-n-butylphosphine. Compounds 39-41, in which the N-1 side chain is rigidified by incorporation of an E-configured double bond, were obtained by palladium(0)-catalyzed coupling of several different 6-(arylthio)uracil derivatives (37, 38) with allyl acetates 33. Compounds 13, 40a,c,d,f, and 41, incorporating an aromatic ring at the end of the acyclic side chain, were found to be more potent than the known diphenyl-substituted HEPT analog BPT (2), two of them, 40c,d, being 10-fold more active.