Evaluation of the Biological Activity of Manna Exudate, from Fraxinus ornus L., and Its Potential Use as Hydrogel Formulation in Dermatology and Cosmetology.

Manna, a well-known herbal drug has multiple traditional and pharmaceutical uses and the entire composition, sugar derivatives and polyphenols, gives rise to a very interesting bioactive complex with versatile therapeutic and benefic properties such as antioxidant and anti-inflammatory activities. The aim of this research was to investigate a F. ornus manna extract loaded in a pectin hydrogel as a synergic vehicle to evaluate the potential use of the complex for cosmetic and dermatological applications. In particular, the study set out to disclose manna properties as a wound healing agent with antimicrobial and reparative activity on infected tissues. Moreover, considering the correlation between antioxidant activity and antiaging potential, the extract was investigated in regard to the anti-elastase activity and skin whitening potential. The total phenolic content of each extract was also determined and a safe profile by in vitro cytotoxicity studies was verified. The hydrogel complex, containing the manna extract and pectin as the gelling agent, exhibited suitable properties in terms of pH (from 5.50 to 6.80), rheological behavior and ability of preserving the antioxidant activity of the manna exudate (around 10%). All the peculiarities that make the pectin hydrogels ideal systems for skin disease, as wound dressings and for antiaging cosmetic formulations.

Investigations of Antioxidant and Anti-Cancer Activities of 5-Aminopyrazole Derivatives.

To further extend the structure-activity relationships (SARs) of 5-aminopyrazoles (5APs) and identify novel compounds able to interfere with inflammation, oxidative stress, and tumorigenesis, 5APs 1-4 have been designed and prepared. Some chemical modifications have been inserted on cathecol function or in aminopyrazole central core; in detail: (i) smaller, bigger, and more lipophilic substituents were introduced in meta and para positions of catechol portion (5APs 1); (ii) a methyl group was inserted on C3 of the pyrazole scaffold (5APs 2); (iii) a more flexible alkyl chain was inserted on N1 position (5APs 3); (iv) the acylhydrazonic linker was moved from position 4 to position 3 of the pyrazole scaffold (5APs 4). All new derivatives 1-4 have been tested for radical scavenging (DPPH assay), anti-aggregating/antioxidant (in human platelets) and cell growth inhibitory activity (MTT assay) properties. In addition, in silico pharmacokinetics, drug-likeness properties, and toxicity have been calculated. 5APs 1 emerged to be promising anti-proliferative agents, able to suppress the growth of specific cancer cell lines. Furthermore, derivatives 3 remarkably inhibited ROS production in platelets and 5APs 4 showed interesting in vitro radical scavenging properties. Overall, the collected results further confirm the pharmaceutical potentials of this class of compounds and support future studies for the development of novel anti-proliferative and antioxidant agents.

Structure-Activity Relationship Studies on Highly Functionalized Pyrazole Hydrazones and Amides as Antiproliferative and Antioxidant Agents.

Aminopyrazoles represent interesting structures in medicinal chemistry, and several derivatives showed biological activity in different therapeutic areas. Previously reported 5-aminopyrazolyl acylhydrazones and amides showed relevant antioxidant and anti-inflammatory activities. To further extend the structure-activity relationships in this class of derivatives, a novel series of pyrazolyl acylhydrazones and amides was designed and prepared through a divergent approach. The novel compounds shared the phenylamino pyrazole nucleus that was differently decorated at positions 1, 3, and 4. The antiproliferative, antiaggregating, and antioxidant properties of the obtained derivatives 10-22 were evaluated in in vitro assays. Derivative 11a showed relevant antitumor properties against selected tumor cell lines (namely, HeLa, MCF7, SKOV3, and SKMEL28) with micromolar IC50 values. In the platelet assay, selected pyrazoles showed higher antioxidant and ROS formation inhibition activity than the reference drugs acetylsalicylic acid and N-acetylcysteine. Furthermore, in vitro radical scavenging screening confirmed the good antioxidant properties of acylhydrazone molecules. Overall, the collected data allowed us to extend the structure-activity relationships of the previously reported compounds and confirmed the pharmaceutical attractiveness of this class of aminopyrazole derivatives.

New Pyrazolyl Thioureas Active against the Staphylococcus Genus.

To meet the urgent need for new antibacterial molecules, a small library of pyrazolyl thioureas (PTUs) was designed, synthesized and tested against difficult-to-treat human pathogens. The prepared derivatives are characterized by a carboxyethyl functionality on C4 and different hydroxyalkyl chains on N1. Compounds 1a-o were first evaluated against a large panel of Gram-positive and Gram-negative pathogens. In particular, the majority of PTUs proved to be active against different species of the Staphylococcus genus, with MIC values ranging from 32 to 128 µg/mL on methicillin-resistant Staphylococcus strains, often responsible for severe pulmonary disease in cystic fibrosis patients. Time-killing experiments were also performed for the most active compounds, evidencing a bacteriostatic mechanism of action. For most active derivatives, cytotoxicity was evaluated in Vero cells, and at the tested concentrations and at the experimental exposure time of 24 h, none of the compounds analysed showed significant toxicity. In addition, favourable drug-like, pharmacokinetic and toxicity properties were predicted for all new synthesized derivatives. Overall, the collected data confirmed the PTU scaffold as a promising chemotype for the development of novel antibacterial agents active against Gram-positive multi-resistant strains frequently isolated from cystic fibrosis patients.

Antimicrobial Peptides and Cationic Nanoparticles: A Broad-Spectrum Weapon to Fight Multi-Drug Resistance Not Only in Bacteria.

In the last few years, antibiotic resistance and, analogously, anticancer drug resistance have increased considerably, becoming one of the main public health problems. For this reason, it is crucial to find therapeutic strategies able to counteract the onset of multi-drug resistance (MDR). In this review, a critical overview of the innovative tools available today to fight MDR is reported. In this direction, the use of membrane-disruptive peptides/peptidomimetics (MDPs), such as antimicrobial peptides (AMPs), has received particular attention, due to their high selectivity and to their limited side effects. Moreover, similarities between bacteria and cancer cells are herein reported and the hypothesis of the possible use of AMPs also in anticancer therapies is discussed. However, it is important to take into account the limitations that could negatively impact clinical application and, in particular, the need for an efficient delivery system. In this regard, the use of nanoparticles (NPs) is proposed as a potential strategy to improve therapy; moreover, among polymeric NPs, cationic ones are emerging as promising tools able to fight the onset of MDR both in bacteria and in cancer cells.

Valorization and Potential Antimicrobial Use of Olive Mill Wastewater (OMW) from Italian Olive Oil Production.

The production of olive oil generates olive mill wastewater (OMW) which essentially derives from the processing, treatment and pressing of olives in mills. Traditional milling processes require a quantity of water varying between 40 and 120 L per quintal of pressed olives, generating a considerable amount of wastewater. It is thus necessary to reduce process water and enhance its use to implement the concept of a circular economy. To this end, our preliminary work was dedicated to water purification by means of suitable and efficient filtration systems. The microfiltered OMW was firstly concentrated through reverse osmosis. Then, an additional concentration step was carried out via vacuum membrane distillation using hydrophobic hollow fiber membranes. The application of the membrane-based processes allowed the recovery of a purified water and the concentration of valuable polyphenols in a smaller volume. The different fractions obtained from the purification have been tested for the determination of the antioxidant power (DPPH assay) and dosage of polyphenols (Folin-Ciocalteu assay) and were characterized using IR spectroscopy. All samples showed relevant antioxidant activity (percentage range: 10-80%) and total phenolic content in the 1.5-15 g GAE/L range. The obtained fractions were tested for their antimicrobial effect on numerous clinical isolates of Gram-positive and Gram-negative species, resistant and multi-resistant to current antibiotic drugs. OMW samples showed widespread activity against the considered (phyto)pathogens (MIC range 8-16 mg/mL) thus supporting the value of this waste material in the (phyto)pharmaceutical field.

Bactericidal Activity of Non-Cytotoxic Cationic Nanoparticles against Clinically and Environmentally Relevant Pseudomonas spp. Isolates.

Difficult-to-treat bacterial infections caused by resistant human and plant pathogens severely afflict hospitals, and concern the agri-food sectors. Bacteria from the Pseudomonadaceae family, such as P. aeruginosa, P. putida, P. fluorescens, and P. straminea, can be responsible for severe nosocomial infections in humans. P. fragi is the major cause of dairy and meat spoilage, while P. syringae can infect a wide range of economically important plant species, including tobacco, kiwi, and tomato. Therefore, a cationic water-soluble lysine dendrimer (G5-PDK) was tested on several species of Pseudomonas genus. Interestingly, G5-PDK demonstrated variable minimum inhibitory concentrations (MICs), depending on their pigment production, on Pseudomonas aeruginosa (1.6-> 6.4 µM), MICs = 3.2-6.4 µM on P. putida clinical isolates producing pyoverdine, and very low MICs (0.2-1.6 µM) on strains that produced non-pigmented colonies. Time-kill experiments established the rapid bactericidal activity of G5-PDK. In the cytotoxicity experiments on human keratinocytes, after 4 h of treatment with G5-PDK at concentrations 16-500 × MIC, more than 80% of viable cells were observed, and after 24 h, the selectivity indices were maintained above the maximum value reported as acceptable. Due to its proven bactericidal potency and low cytotoxicity, G5-PDK should be seriously considered to counteract clinically and environmentally relevant Pseudomonas isolates.