Verification of the Self-Healing Ability of PP-co-HUPy Copolymers in Epoxy Systems.

This work concerns the verification of the self-healing ability of PP-co-HUPy copolymers dispersed in epoxy systems. PP is the acronym for the Poly-PEGMA polymer, and HUPy refers to the HEMA-UPy copolymers based on ureidopyrimidinone (UPy) moieties. In particular, this work aims to verify whether this elastomer characterized by an intrinsic self-healing ability can activate supramolecular interactions among polymer chains of an epoxy resin, as in the elastomer alone. The elastomer includes a class of polyethylene glycol monomethyl ether methacrylate-based copolymers, with different percentages of urea-N-2-amino-4-hydroxy-6-methyl pyrimidine-N'-(hexamethylene-n-carboxyethyl methacrylate) (HEMA-UPy) co-monomers. The self-healing capability of these copolymers based on possible quadruple hydrogen bond interactions between polymer chains has been verified. The formulated epoxy samples did not show self-healing efficiency. This can be attributed to the formation of phase segregation that originates during the curing process of the samples, although the PP-co-HUPy copolymers are completely soluble in the liquid epoxy matrix EP. The morphological investigation highlighted the presence of crystals of PP-co-HUPy copolymers, which are in greater quantity in the sample containing the highest weight percentage (7.8 wt%) of HUPy units. Furthermore, the crystals act as promotors for increasing the curing degree (DC) of the epoxy systems containing HUPy units. DC goes from 91.6% for EP to 96.1% and 95.4% for the samples containing weight percentages of 2.5 and 7.8 wt% of HUPy units, respectively. Dynamic mechanical analysis (DMA) shows storage modulus values for epoxy systems containing PP-co-HUPy units lower than that of the unfilled resin EP. The values of maximum in Tan δ (Tg), representing the temperature at which the glass transition occurs, are 220 for the unfilled resin EP, 228 for the sample containing 2.5 wt% of HEMA-UPy units, and 211 for the sample containing 7.8 wt% of HEMA-UPy units.

Silver and Gold Complexes with NHC-Ligands Derived from Caffeine: Catalytic and Pharmacological Activity.

N-heterocyclic carbene (NHC) silver(I) and gold(I) complexes have found different applications in various research fields, as in medicinal chemistry for their antiproliferative, anticancer, and antibacterial activity, and in chemistry as innovative and effective catalysts. The possibility of modulating the physicochemical properties, by acting on their ligands and substituents, makes them versatile tools for the development of novel metal-based compounds, mostly as anticancer compounds. As it is known, chemotherapy is commonly adopted for the clinical treatment of different cancers, even though its efficacy is hampered by several factors. Thus, the development of more effective and less toxic drugs is still an urgent need. Herein, we reported the synthesis and characterization of new silver(I) and gold(I) complexes stabilized by caffeine-derived NHC ligands, together with their biological and catalytic activities. Our data highlight the interesting properties of this series as effective catalysts in A3-coupling and hydroamination reactions and as promising anticancer, anti-inflammatory, and antioxidant agents. The ability of these complexes in regulating different pathological aspects, and often co-promoting causes, of cancer makes them ideal leads to be further structurally functionalized and investigated.

A Comprehensive Review on the State of the Art of Breast Cancers in Italy.

Breast cancer (BC) currently represents one of the most prevalent cancers among women worldwide and the leading cause of cancer death among women, also negatively affecting the quality of life (QoL) in patients. Over the past two decades, BC research has led to extraordinary advances in our understanding of the disease, resulting in more effective treatments. However, its occurrence is still increasing. Several new treatments are now under development worldwide, but they are not devoid of wellknown side effects, and a great number of patients develop endocrine resistance. Nevertheless, the design and synthesis of more suitable strategies and new drugs to treat breast cancers, overcome resistance and side effects, and obtain better therapeutic outcomes are needed. In this review, we summarize the therapies and the clinical studies currently ongoing in Italy for the treatment of BCs, mainly HER2+ MBC, HER2-low MBC, and TNBC, focusing on the most recent ones, also in consideration of diverse facets, including some aspects related to QoL. Finally, some studies related to the usefulness of physical activity in BC will be cited.

Complexes of Ruthenium(II) as Promising Dual-Active Agents against Cancer and Viral Infections.

Poor responses to medical care and the failure of pharmacological treatment for many high-frequency diseases, such as cancer and viral infections, have been widely documented. In this context, numerous metal-based substances, including cisplatin, auranofin, various gold metallodrugs, and ruthenium complexes, are under study as possible anticancer and antiviral agents. The two Ru(III) and Ru(II) complexes, namely, BOLD-100 and RAPTA-C, are presently being studied in a clinical trial and preclinical studies evaluation, respectively, as anticancer agents. Interestingly, BOLD-100 has also recently demonstrated antiviral activity against SARS-CoV-2, which is the virus responsible for the COVID-19 pandemic. Over the last years, much effort has been dedicated to discovering new dual anticancer-antiviral agents. Ru-based complexes could be very suitable in this respect. Thus, this review focuses on the most recent studies regarding newly synthesized Ru(II) complexes for use as anticancer and/or antiviral agents.

Hydroamination of alkynes catalyzed by NHC-Gold(I) complexes: the non-monotonic effect of substituted arylamines on the catalyst activity.

Imines are valuable key compounds for synthesizing several nitrogen-containing molecules used in biological and industrial fields. They have been obtained, as highly regioselective Markovnikov products, by reacting several alkynes with arylamines in the presence of three new N-Heterocyclic carbene gold(I) complexes (3b, 4b, and 6b) together with the known 1-2b and 7b gold complexes as well as silver complexes 1-2a. Gold(I) complexes were investigated by means of NMR, mass spectroscopy, elemental analysis, and X-ray crystallographic studies. Accurate screening of co-catalysts and solvents led to identifying the best reaction conditions and the most active catalyst (2b) in the model hydroamination of phenylacetylene with aniline. Complex 2b was then tested in the hydroamination of alkynes with a wide variety of arylamines yielding a lower percentage of product when arylamines with both electron-withdrawing and electron-donating substituents were involved. Computational studies on the rate-determining step of hydroamination were conducted to shed light on the significantly different yields observed when reacting arylamines with different substituents.

NHC-Ag(I) and NHC-Au(I) Complexes with N-Boc-Protected α-Amino Acidate Counterions Powerfully Affect the Growth of MDA-MB-231 Cells.

N-Heterocyclic carbene (NHC) metal complexes are attracting scientists' interest as an alluring class of metallodrugs. Indeed, the versatile functionalization of NHC ligands makes them optimal scaffolds to be developed in medicinal chemistry. Besides, amino acids are great biological ligands for metals, such as silver and gold, even though their use is still under-investigated. Aiming to shed light on the anticancer properties of this kind of complex, we investigated a series of silver and gold complexes, stabilized by NHC ligands and bearing carboxylate salts of tert-butyloxycarbonyl (Boc)-N-protected glycine and l-phenylalanine as anionic ligands. The most active complexes, AuM1Gly and AuM1Phe, powerfully affect the growth of MDA-MB-231 breast cancer cells, with IC50 values in the low nanomolar range. Further studies demonstrated the blockade of the human topoisomerase I activity and actin polymerization reaction at 0.001 µM. These unique features make these complexes very interesting and worthy to be used for future in vivo studies.

Mechano Chemical Compatibilization of Polyethylene with Graphite by Means of a Suitable Ester.

An effective non-covalent compatibilization method for graphite and low-density polyethylene is reported. To obtain this result, pyren-1-yl-stearate (P1S) was synthesized, characterized and mixed with graphite to provide a better dispersion in polyethylene matrix. The P1S improves the dispersion of carbon filler in polyethylene through non-covalent compatibilization: the pyrenyl group gives π-π stacking interactions with graphite and the stearyl chain provides van der Waals interaction with the polymer chain (specifically London dispersion forces). In this study, different P1S/graphite fillers were prepared with a ratio by weight of 90/10 and 50/50, respectively, by using manual and ball-milling mixing. Their stability, interaction and morphology were evaluated through TGA, RX, and SEM. Thermogravimetric analyses showed that ball-milling mixing is more effective than manual mixing in promoting π-π stacking interactions of molecules such as P1S ester containing an alkyl chain and aromatic rings. The role of ball milling is confirmed by X-ray diffraction measurements since it was possible to observe both exfoliation and intercalation phenomena when this technique was used to mix the P1S ester with graphite. SEM analyses of polyethylene containing 1% of the carbon fillers again highlighted the importance of ball milling to promote the interaction of the ester with graphite and, simultaneously, the importance of the alkyl chain in order to achieve polyethylene-graphite compatibilization.

Activity and Selectivity of Novel Chemical Metallic Complexes with Potential Anticancer Effects on Melanoma Cells.

Human malignant melanoma cells from lymph node metastatic site (MeWo) were selected for testing several synthesized and purified silver(I) and gold(I) complexes stabilized by unsymmetrically substituted N-heterocyclic carbene (NHC) ligands, called L20 (N-methyl, N'-[2-hydroxy ethylphenyl]imidazol-2-ylide) and M1 (4,5-dichloro, N-methyl, N'-[2-hydroxy ethylphenyl]imidazol-2-ylide), having halogenide (Cl- or I-) or aminoacyl (Gly=N-(tert-Butoxycarbonyl)glycinate or Phe=(S)-N-(tert-Butoxycarbonyl)phenylalaninate) counterion. For AgL20, AuL20, AgM1 and AuM1, the Half-Maximal Inhibitory Concentration (IC50) values were measured, and all complexes seemed to reduce cell viability more effectively than Cisplatin, selected as control. The complex named AuM1 was the most active just after 8 h of treatment at 5 µM, identified as effective growth inhibition concentration. AuM1 also showed a linear dose and time-dependent effect. Moreover, AuM1 and AgM1 modified the phosphorylation levels of proteins associated with DNA lesions (H2AX) and cell cycle progression (ERK). Further screening of complex aminoacyl derivatives indicated that the most powerful were those indicated with the acronyms: GlyAg, PheAg, AgL20Gly, AgM1Gly, AuM1Gly, AgL20Phe, AgM1Phe, AuM1Phe. Indeed, the presence of Boc-Glycine (Gly) and Boc-L-Phenylalanine (Phe) showed an improved efficacy of Ag main complexes, as well as that of AuM1 derivatives. Selectivity was further checked on a non-cancerous cell line, a spontaneously transformed aneuploid immortal keratinocyte from adult human skin (HaCaT). In such a case, AuM1 and PheAg complexes resulted as the most selective allowing HaCaT viability at 70 and 40%, respectively, after 48 h of treatment at 5 µM. The same complexes tested on 3D MeWo static culture induced partial spheroid disaggregation after 24 h of culture, with almost half of the cells dead.

Synthesis of Novel N-Heterocyclic Carbene-Ruthenium (II) Complexes, "Precious" Tools with Antibacterial, Anticancer and Antioxidant Properties.

Ruthenium N-heterocyclic carbene (Ru-NHC) complexes show interesting physico-chemical properties as catalysts and potential in medicinal chemistry, exhibiting multiple biological activities, among them anticancer, antimicrobial, antioxidant, and anti-inflammatory. Herein, we designed and synthesized a new series of Ru-NHC complexes and evaluated their biological activities as anticancer, antibacterial, and antioxidant agents. Among the newly synthesized complexes, RANHC-V and RANHC-VI are the most active against triple-negative human breast cancer cell lines MDA-MB-231. These compounds were selective in vitro inhibitors of the human topoisomerase I activity and triggered cell death by apoptosis. Furthermore, the Ru-NHC complexes' antimicrobial activity was studied against Gram-positive and -negative bacteria, revealing that all the complexes possessed the best antibacterial activity against the Gram-positive Staphylococcus aureus, at a concentration of 25 µg/mL. Finally, the antioxidant effect was assessed by DPPH and ABTS radicals scavenging assays, resulting in a higher ability for inhibiting the ABTS•+, with respect to the well-known antioxidant Trolox. Thus, this work provides encouraging insights for further development of novel Ru-NHC complexes as potent chemotherapeutic agents endowed with multiple biological properties.

Nebulization of pharmacological solutions with an innovative medical device based on microvaporization.

The currently available nebulization devices have a slow aerosol flow and produce vapor with large microdrops. Improved devices that achieve higher airflow and produce smaller microdrops are needed to improve the clinical care of patients. To address this critical need, we developed a novel system for the molecular vaporization of liquids. This device vaporizes an active pharmacological substance dissolved in water, alcohol, or a mixture of water and alcohol using two energy sources at the same time: high-frequency ultrasound and thermal induction. Application of energy to a solution contained in the device's tank allows, within tens of seconds, for the vaporization of the solution itself, with the generation of a vapor consisting of microdrops of very small diameter (0.2-0.3 µm). In this article, we illustrate the technology used, the main verification tests performed, and the primary fields of application for this device. In particular, the advantages of both the aerosol delivery system and the administration system are highlighted.

5,8-Dimethyl-9H-carbazole Derivatives Blocking hTopo I Activity and Actin Dynamics.

Over the years, carbazoles have been largely studied for their numerous biological properties, including antibacterial, antimalarial, antioxidant, antidiabetic, neuroprotective, anticancer, and many more. Some of them have gained great interest for their anticancer activity in breast cancer due to their capability in inhibiting essential DNA-dependent enzymes, namely topoisomerases I and II. With this in mind, we studied the anticancer activity of a series of carbazole derivatives against two breast cancer cell lines, namely the triple negative MDA-MB-231 and MCF-7 cells. Compounds 3 and 4 were found to be the most active towards the MDA-MB-231 cell line without interfering with the normal counterpart. Using docking simulations, we assessed the ability of these carbazole derivatives to bind human topoisomerases I and II and actin. In vitro specific assays confirmed that the lead compounds selectively inhibited the human topoisomerase I and interfered with the normal organization of the actin system, triggering apoptosis as a final effect. Thus, compounds 3 and 4 are strong candidates for further drug development in multi-targeted therapy for the treatment of triple negative breast cancer, for which safe therapeutic regimens are not yet available.

Biological Activities of Ruthenium NHC Complexes: An Update.

Ruthenium N-heterocyclic carbene (NHC) complexes have unique physico-chemical properties as catalysts and a huge potential in medicinal chemistry and pharmacology, exhibiting a variety of notable biological activities. In this review, the most recent studies on ruthenium NHC complexes are summarized, focusing specifically on antimicrobial and antiproliferative activities. Ruthenium NHC complexes are generally active against Gram-positive bacteria, such as Bacillus subtilis, Staphylococcus aureus, Micrococcus luteus, Listeria monocytogenes and are seldom active against Gram-negative bacteria, including Salmonella typhimurium, Pseudomonas aeruginosa and Escherichia coli and fungal strains of Candida albicans. The antiproliferative activity was tested against cancer cell lines of human colon, breast, cervix, epidermis, liver and rat glioblastoma cell lines. Ruthenium NHC complexes generally demonstrated cytotoxicity higher than standard anticancer drugs. Further studies are needed to explore the mechanism of action of these interesting compounds.

Diarylureas: New Promising Small Molecules against Streptococcus mutans for the Treatment of Dental Caries.

Dental caries is a biofilm-mediated disease that represents a worldwide oral health issue. Streptococcus mutans has been ascertained as the main cariogenic pathogen responsible for human dental caries, with a high ability to form biofilms, regulated by the quorum sensing. Diarylureas represent a class of organic compounds that show numerous biological activities, including the antimicrobial one. Two small molecules belonging to this class, specifically to diphenylureas, BPU (1,3-bis[3,5-bis(trifluoromethyl)phenyl]urea) and DMTU (1,3-di-m-tolyl-urea), showed interesting results in studies regarding the antimicrobial activity against the cariogenic bacterium S. mutans. Since there are not many antimicrobials used for the prevention and treatment of caries, further studies on these two interesting compounds and other diarylureas against S. mutans may be useful to design new effective agents for the treatment of caries with generally low cytotoxicity.

Metal Complexes with Schiff Bases: Data Collection and Recent Studies on Biological Activities.

Metal complexes play a crucial role in pharmaceutical sciences owing to their wide and significant activities. Schiff bases (SBs) are multifaceted pharmacophores capable of forming chelating complexes with various metals in different oxidation states. Complexes with SBs are extensively studied for their numerous advantages, including low cost and simple synthetic strategies. They have been reported to possess a variety of biological activities, including antimicrobial, anticancer, antioxidant, antimalarial, analgesic, antiviral, antipyretic, and antidiabetic ones. This review summarizes the most recent studies on the antimicrobial and antiproliferative activities of SBs-metal complexes. Moreover, recent studies regarding mononuclear and binuclear complexes with SBs are described, including antioxidant, antidiabetic, antimalarial, antileishmanial, anti-Alzheimer, and catecholase activities.

Drugs for COVID-19: An Update.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was the seventh known human coronavirus, and it was identified in Wuhan, Hubei province, China, in 2020. It caused the highly contagious disease called coronavirus disease 2019 (COVID-19), declared a global pandemic by the World Health Organization (WHO) on 11 March 2020. A great number of studies in the search of new therapies and vaccines have been carried out in these three long years, producing a series of successes; however, the need for more effective vaccines, therapies and other solutions is still being pursued. This review represents a tracking shot of the current pharmacological therapies used for the treatment of COVID-19.

Exploring the anticancer and antioxidant properties of Vicia faba L. pods extracts, a promising source of nutraceuticals.

Background: Pulse crops are considered the major sources of proteins, dietary fiber, micronutrients, and bioactive phytochemicals. Among the numerous pulse crops, broad beans (Vicia faba L.) have received particular attention due to their nutraceutical, functional and economic importance. Our attention was mainly focused on the broad bean pods (VFs), which are the primary by-product of the domestic and industrial processing of broad beans and an attractive source of valuable ingredients. Methods: In order to investigate the VFs properties, the flours from broad beans of three different harvest periods were extracted with acetone, methanol and 70% aqueous ethanol and the dried extracts were analyzed, qualitatively and quantitatively, and tested for their antioxidant through DPPH and ABTS assay and anticancer activities using the MTT assay and immunofluorescence analysis. Results: The VF extracts demonstrated a good in vitro radical scavenging activity from the first stage of collection of all the V. faba L. extracts. Additionally, the extracts were tested for their cytotoxicity against a panel of cancer and normal cells and the outcomes indicated the ethanol extract as the most active against the melanoma cell line Sk-Mel-28, without affecting the viability of the normal cells. Finally, we found out that the ethanol extract interfered with the microtubules organization, leading to the cancer cells death by apoptosis.

Thidiazuron: New Trends and Future Perspectives to Fight Xylella fastidiosa in Olive Trees.

These days, most of our attention has been focused on the COVID-19 pandemic, and we have often neglected what is happening in the environment. For instance, the bacterium Xylella fastidiosa re-emerged as a plant pathogen of global importance in 2013 when it was first associated with an olive tree disease epidemic in Italy, called Olive Quick Decline Syndrome (OQDS), specifically caused by X. fastidiosa subspecies pauca ST53, which affects the Salento olive trees (Apulia, South-East Italy). This bacterium, transmitted by the insect Philaenus spumarius, is negatively reshaping the Salento landscape and has had a very high impact in the production of olives, leading to an increase of olive oil prices, thus new studies to curb this bacterium are urgently needed. Thidiazuron (TDZ), a diphenylurea (N-phenyl-1,2,3-thiadiazol-5-yl urea), has gained considerable attention in recent decades due to its efficient role in plant cell and tissue culture, being the most suitable growth regulator for rapid and effective plant production in vitro. Its biological activity against bacteria, fungi and biofilms has also been described, and the use of this low-cost compound to fight OQDS may be an intriguing idea.

N-Heterocyclic Carbene (NHC) Silver Complexes as Versatile Chemotherapeutic Agents Targeting Human Topoisomerases and Actin.

In recent years, the number of people suffering from cancer has risen rapidly and the World Health Organization and U.S. and European governments have identified this pathology as a priority issue. It is known that most bioactive anticancer molecules do not target a single protein but exert pleiotropic effects, simultaneously affecting multiple pathways. In our study, we designed and synthesized a new series of silver N-heterocyclic carbene (NHC) complexes [(NHC)2 Ag]+ [AgX2 ]- (X=iodide or acetate). The new complexes were active against two human breast cancer cell lines, MCF-7 and MDA-MB-231. These compounds showed multiple target actions as anticancer, by inhibiting in vitro the activity of the human topoisomerases I and II and interfering with the cytoskeleton dynamic, as also confirmed by in silico studies. Moreover, the antimicrobial activity of these silver complexes was studied against Gram-positive/negative bacteria. These dual properties provide a two-tiered approach, making these compounds of interest to be further deepened for the development of new chemotherapeutic agents.

Electrospun Membranes Designed for Burst Release of New Gold-Complexes Inducing Apoptosis of Melanoma Cells.

Two non-commercial metallic Au-based complexes were tested against one of the most aggressive malignant melanomas of the skin (MeWo cells), through cell viability and time-lapse live-cell imaging system assays. The tests with the complexes were carried out both in the form of free metallic complexes, directly in contact with the MeWo cell line culture, and embedded in fibers of Polycaprolactone (PCL) membranes produced by the electrospinning technique. Membranes functionalized with complexes were prepared to evaluate the efficiency of the membranes against the melanoma cells and therefore their feasibility in the application as an antitumoral patch for topical use. Both series of tests highlighted a very effective antitumoral activity, manifesting a very relevant cell viability inhibition after both 24 h and 48 h. In the case of the AuM1 complex at the concentration of 20 mM, melanoma cells completely died in this short period of time. A mortality of around 70% was detected from the tests performed using the membranes functionalized with AuM1 complex at a very low concentration (3 wt.%), even after 24 h of the contact period. The synthesized complexes also manifest high selectivity with respect to the MeWo cells. The peculiar structural and morphological organization of the nanofibers constituting the membranes allows for a very effective antitumoral activity in the first 3 h of treatment. Experimental points of the release profiles were perfectly fitted with theoretical curves, which easily allow interpretation of the kinetic phenomena occurring in the release of the synthesized complexes in the chosen medium.

Triclosan: A Small Molecule with Controversial Roles.

Triclosan (TCS), a broad-spectrum antimicrobial agent, has been widely used in personal care products, medical products, plastic cutting boards, and food storage containers. Colgate Total® toothpaste, containing 10 mM TCS, is effective in controlling biofilm formation and maintaining gingival health. Given its broad usage, TCS is present ubiquitously in the environment. Given its strong lipophilicity and accumulation ability in organisms, it is potentially harmful to biohealth. Several reports suggest the toxicity of this compound, which is inserted in the class of endocrine disrupting chemicals (EDCs). In September 2016, TCS was banned by the U.S. Food and Drug Administration (FDA) and the European Union in soap products. Despite these problems, its application in personal care products within certain limits is still allowed. Today, it is still unclear whether TCS is truly toxic to mammals and the adverse effects of continuous, long-term, and low concentration exposure remain unknown. Indeed, some recent reports suggest the use of TCS as a repositioned drug for cancer treatment and cutaneous leishmaniasis. In this scenario it is necessary to investigate the advantages and disadvantages of TCS, to understand whether its use is advisable or not. This review intends to highlight the pros and cons that are associated with the use of TCS in humans.