Marine Alkaloid 2,2-Bis(6-bromo-3-indolyl) Ethylamine and Its Synthetic Derivatives Inhibit Microbial Biofilms Formation and Disaggregate Developed Biofilms

The antimicrobial activity of the marine bisindole alkaloid 2,2-bis(6-bromo-3-indolyl) ethylamine (1) and related synthetic analogues (compounds 2–8) against target microorganisms was investigated by Minimum Inhibitory Concentration (MIC) determination. Compound 1 showed the greatest antimicrobial activity with the lowest MIC (8 mg/L) against Escherichia coli, Staphylococcus aureus, and Klebsiella pneumoniae, while the derivatives exhibited higher MICs values (from 16 to 128 mg/L). Compounds 1, 3, 4, and 8, the most active ones, were then tested against E. coli, S. aureus, K. pneumoniae, and Candida albicans during biofilms formation as well as on 24 h developed biofilms. The natural alkaloid 1 inhibited the biofilm formation of all the tested microorganisms up to 82.2% and disaggregated biofilms of E. coli, S. aureus, K. pneumoniae, and C. albicans after 30 min of contact, as assessed by viable plate count and crystal violet (CV) staining (optical density at 570 nm). Synthetic derivatives 3, 4, and 8 displayed anti-biofilm activity toward individual bacterial populations. This study highlights the potential of marine bisindole alkaloid 1 as anti-biofilm agent and shows, through a preliminary structure activity relationship (SAR), the importance of halogens and ethylamine side chain for the antimicrobial and antibiofilm activities of this bisindole series

Synthesis and Evaluation of Saccharide-Based Aliphatic and Aromatic Esters as Antimicrobial and Antibiofilm Agents

A small library of sugar-based (i.e., glucose, mannose and lactose) monoesters containing hydrophobic aliphatic or aromatic tails were synthesized and tested. The antimicrobial activity of the compounds against a target panel of Gram-positive, Gram-negative and fungi was assessed. Based on this preliminary screening, the antibiofilm activity of the most promising molecules was evaluated at different development times of selected food-borne pathogens (E. coli, L. monocytogenes, S. aureus, S. enteritidis). The antibiofilm activity during biofilm formation resulted in the following: mannose C10 > lactose biphenylacetate > glucose C10 > lactose C10. Among them, mannose C10 and lactose biphenylacetate showed an inhibition for E. coli 97% and 92%, respectively. At MICs values, no toxicity was observed on Caco-2 cell line for all the examined compounds. Overall, based on these results, all the sugar-based monoesters showed an interesting profile as safe antimicrobial agents. In particular, mannose C10 and lactose biphenylacetate are the most promising as possible biocompatible and safe preservatives for pharmaceutical and food applications

lactose based fatty acid monoesters synthesis antimicrobial activity and permeability enhancement studies

We present the synthesis and the in vitro assaying of a series of lactose-based non-ionic surfactants, highlighting the relationship between their structure and biological effect. Using tensiometric measurements the critical micelle concentrations (CMCs) of the surfactants were determined and demonstrate that increasing hydrophobic chain length reduces surfactant CMC. In vitro testing on Caco-2 intestinal and Calu-3 airway epithelia revealed that cytotoxicity is present, for most of the surfactants, at concentrations greater than their CMCs. Importantly, through the culture of epithelial monolayers on Transwell® supports, the surfactants demonstrate the ability to reversibly modulate transepithelial electrical resistance (TEER), and thus open tight junctions, at non-toxic concentrations. The surfactants were then tested for their ability to improve the in vitro permeability of Ovalbumin and Dextran, confirming their potential application as safe permeability enhancers in vivo. Moreover, the synthesized compounds exhibit antimicrobial activity versus eight pathogenic species belonging to Gram-positive, Gram-negative microorganisms and fungi

6'-O-Lactose Ester Surfactants as an Innovative Opportunity in the Pharmaceutical Field: From Synthetic Methods to Biological Applications

Glycolipid surfactants are biocompatible and biodegradable compounds characterized by potential applications in various sectors including pharmaceuticals, cosmetics, agriculture, and food production. A specific overview regarding synthetic methodologies and properties of 6'-lactose-based surfactants is presented herein, particularly all the synthetic approaches to this class of lactose esters, such as enzymatic and traditional organic syntheses. Moreover, detailed descriptions of physicochemical data and biocompatibility properties of these molecules, that is, surface tension, critical micelle concentration, emulsifying ability, foaming, particle size distribution, biocompatibility, and safety, are described. Biological applications with a focus on permeability enhancing, antimicrobial activity, and antibiofilm properties of 6'-lactose-based esters are also reported

Organocatalytic synthesis of α-quaternary amino acid derivatives via aza-Friedel–Crafts alkylation of indoles with simple α-amidoacrylates

none4The first (organo)catalytic method for regio- and chemoselective aza-Friedel-Crafts (FC) alkylation of indoles and pyrroles with commercially available methyl alpha-acetamidoacrylates has been discovered. It minimizes/eliminates common competing reactions that occur due to the high and multiatom-nucleophilic character of indole and pyrrole. Diverse quaternary alpha-amino acids were successfully prepared in good yield and high selectivity using low catalyst loading. The enantioselective variant using BINOL-derived phosphoric acids was also explored with indole providing the desired F-C alkylation product with moderate enantioselectivities.openRIGHI M.; BARTOCCINI F.; LUCARINI S.; PIERSANTI G.Righi, M.; Bartoccini, Francesca; Lucarini, Simone; Piersanti, Giovann

One-Pot Synthesis of Biheterocycles Based on Indole and Azole Scaffolds Using Tryptamines and 1,2-Diaza-1,3-dienes as Building Blocks

partially_open7noThe rapid and expedient assembly of three new classes of biheterocycles of biological interest, viz. indole–imidazoles 4, indole–pyrroles 6 and indole–triazoles 8 was accomplished using different combinations of tryptamines, 1,2-diaza-1,3-dienes, aldehydes, and/or alkynes as readily available building blocks. Twenty-six derivatives were thus prepared in excellent yields (up to 100 %). The products were screened for in-vitro biological studies. Some of these revealed promising anticancer activity against MCF7 and Caco-2 human tumor cell lines.mixedMantenuto, Serena; Lucarini, Simone; De Santi, Mauro; Piersanti, Giovanni; Brandi, Giorgio; Favi, Gianfranco; Mantellini, FabioMantenuto, Serena; Lucarini, Simone; DE SANTI, Mauro; Piersanti, Giovanni; Brandi, Giorgio; Favi, Gianfranco; Mantellini, Fabi

Harry Potter and the SPELL against bullying

The Harry Potter saga has been—and still is—a worldwide phenomenon, attracting the interest of millions of people. Leveraging this success and the potential for the storyline to act as a moral guide, we developed and tested the SPELL, a scientifically-driven anti-bullying intervention based on the Harry Potter novels. The main goal of this intervention was to foster children and adolescents' willingness to intervene in response to bullying episodes. Participants were middle-school students (N = 343, Mage = 12.18 years), who engaged in four sessions designed to raise awareness about bullying, including its forms, roles of the different bullying actors, its consequences and ways to address it. The sessions also focused on psychological constructs identified in the literature as crucial in fostering bystander intervention, namely empathy, moral disengagement and defender self-efficacy. Results revealed that the intervention, when compared with a control condition, was successful in fostering intentions to counteract bullying, with greater empathy and lower moral disengagement being the psychological processes underlying this effect; evidence for self-efficacy was weaker. Our findings suggest that the powerful magic of Harry Potter can help to create a better world for children and adolescents, as future generations. Please refer to the Supporting Information section to find this article's Community and Social Impact Statement

Synthesis and Biological Characterization of the New Glycolipid Lactose Undecylenate (URB1418)

As a follow-up to our previous studies on glycolipid surfactants, a new molecule, that is lactose 6'-O-undecylenate (URB1418), was investigated. To this end, a practical synthesis and studies aimed at exploring its specific properties were carried out. URB1418 showed antifungal activities against Trichophyton rubrum F2 and Candida albicans ATCC 10231 (MIC 512 μg/mL) and no significant antibacterial activity against Staphylococcus aureus and Pseudomonas aeruginosa. At the same time, it presented anti-inflammatory properties, as documented by the dose-dependent reduction in LPS-induced NO release in RAW 264.7 cells, while a low antioxidant capacity in the range of concentrations tested (EC50 > 200 µM) was also observed. Moreover, URB1418 offers the advantage of being more stable than the reference polyunsaturated lactose esters and of being synthesized using a "green" procedure, involving an enzymatic method, high yield and low manufacturing cost. For all these reasons and the absence of toxicity (HaCaT cells), the new glycolipid presented herein could be considered an interesting compound for applications in various fields

Unsaturated fatty acids lactose esters: cytotoxicity, permeability enhancement and antimicrobial activity

Sugar based surfactants conjugated with fatty acid chains are an emerging broad group of highly biocompatible and biodegradable compounds with established and potential future applications in the pharmaceutical, cosmetic and food industries. In this work, we investigated absorption enhancing and antimicrobial properties of disaccharide lactose, mono-esterified with unsaturated fatty acids through an enzymatic synthetic approach. After chemical and cytotoxicity characterizations, their permeability enhancing activity was demonstrated using intestinal Caco-2 monolayers through transepithelial electrical resistance (TEER) and permeability studies. The synthesised compounds, namely lactose palmitoleate (URB1076) and lactose nervonate (URB1077), were shown to exhibit antimicrobial activity versus eight pathogenic species belonging to Gram-positive, Gram-negative microorganisms and fungi