CHOLANE AND LANOSTANE DERIVATIVES: ANTIMICROBIAL EVALUATION

Steroids are natural compounds with several important applications in many fields of research, such as medicinal chemistry, pharmacology, supramolecular chemistry and nanotechnology.In particular, bile acids such as lithocholic acid (LCA) and ursodeoxycholic acid (UDCA) have been considered quite useful as starting points for a rich and different set of medicinal chemistry activities. Besides, the discovery of bioactive ingredients from plants and fungi is always the main target in medicinal chemistry. The lanostane-type triterpenoid 3b-hydroxylanosta-8,24-diene-21-oic acid (Trametenolic acid, TMA) was the main bioactive component of Gloeophyllum odoratum, which was reported to possess widely bioactivities, including tumor cell anti-proliferation effects (for example, human HL-60 leukemia, human KB epidermoid carcinoma, murine L1210 leukemia cells, Caski, HT-3, T-24, etc.), inhibition of enzyme activity (human thrombin, bovine trypsin and so on).Nevertheless, trametenolic acid was scarcely investigated as antimicrobial agent. Structurally, bile acids (LCA and UDCA) and trametenolic acid are similar since they may be regarded as consisting of two components, a rigid steroid nucleus and an aliphatic side chain possessing a carboxyl group. On the basis of these considerations, six new compounds bearing a guanidine moiety in their side chain were synthesized using LCA, UDCA and TMA as starting materials. The parent bile acids, TMA and their resulting derivatives were evaluated for antimicrobial activity against S. aureus, B. subtilis and M. smegmatis. The derivative 3a-hydroxy-23-guanidino-5b-cholane showed the best activity, with MIC values of 12.5 \u3bcM against S. aureus, 5 \u3bcM against B. subtilis and 50 \u3bcM against M. smegmatis. The cytotoxic activity of bile acids, trametenolic acid and derivatives was also evaluated against HT-29 cell lin

Thymus richardii subsp. nitidus (Guss.) Jalas Essential Oil: An Ally against Oral Pathogens and Mouth Health

The genus Thymus L., belonging to the Lamiaceae family, contains about 220 species with a distribution that mainly extends in Europe, northwest Africa, Ethiopia, Asia, and southern Greenland. Due to their excellent biological properties, fresh and/or dried leaves and aerial parts of several Thymus ssp. have been utilized in the traditional medicine of many countries. To evaluate not only the chemical aspects but also the biological properties, the essential oils (EOs), obtained from the pre-flowering and flowering aerial parts of Thymus richardii subsp. nitidus (Guss.) Jalas, endemic to Marettimo Island (Sicily, Italy), were investigated. The chemical composition of the EOs, obtained by classical hydrodistillation and GC-MS and GC-FID analyses, showed the occurrence of similar amounts of monoterpene hydrocarbons, oxygenated monoterpenes, and sesquiterpene hydrocarbons. The main constituents of the pre-flowering oil were β-bisabolene (28.54%), p-cymene (24.45%), and thymol methyl ether (15.90%). The EO obtained from the flowering aerial parts showed as principal metabolites β-bisabolene (17.91%), thymol (16.26%), and limonene (15.59%). The EO of the flowering aerial parts, and its main pure constituents, β-bisabolene, thymol, limonene, p-cymene, and thymol methyl ether were investigated for their antimicrobial activity against oral pathogens and for their antibiofilm and antioxidant properties

Silver (I) n‐heterocyclic carbene complexes: A winning and broad spectrum of antimicrobial properties

The evolution of antibacterial resistance has arisen as the main downside in fighting bacterial infections pushing researchers to develop novel, more potent and multimodal alternative drugs.Silver and its complexes have long been used as antimicrobial agents in medicine due to the lack of silver resistance and the effectiveness at low concentration as well as to their low toxicities compared to the most commonly used antibiotics.N‐Heterocyclic Carbenes (NHCs) have been extensively employed to coordinate transition metals mainly for catalytic chemistry. However, more recently, NHC ligands have been applied as carrier molecules for metals in anticancer applications. In the present study we selected from literature two NHC‐carbene based on acridinescaffoldand detailed nonclassicalpyrazole derived mono NHC‐Ag neutral and bis NHC‐Ag cationic complexes. Their inhibitor effect on bacterial strains Gram‐negative and positivewas evaluated. Imidazolium NHC silver complex containing the acridine chromophore showed effectiveness at extremely low MIC values. Although pyrazole NHC silver complexes are less active than the acridine NHC‐silver, they represent the first example of this class of compounds with antimicrobial properties. Moreover all complexesare not toxic and they show not significant activity againstmammalian cells (Hek lines) after 4 and 24 h. Based on our experimental evidence, we are confident that this promising class of complexes could represent a valuable starting point for developing candidates for the treatment of bacterial infections, delivering great effectiveness and avoiding the development of resistance mechanisms

Bioinspired hybrid eumelanin-TiO2 antimicrobial nanostructures: the key role of organo-inorganic frameworks in tuning eumelanin's biocide action mechanism through membrane interaction

Intrinsic biocide efficacy of eumelanins can be markedly enhanced through a templated formation in the presence of a TiO2-sol, leading to hybrid TiO2-melanin nanostructures. However, mechanisms and processes behind biocide activity still remain poorly understood. This paper discloses the fundamental mechanism of action of these systems providing mechanistic information on their peculiar interaction with Escherichia coli strains. To this purpose biocide characterization is combined with Electron Paramagnetic Resonance (EPR) spectroscopy to investigate radical species produced by the hybrids as well as their interactions with Gram(-) external bacterial membranes. Experimental results indicate that TiO2 mediated eumelanin polymerization leads to a peculiar mechanism of action of hybrid nanostructures, whose strong interactions with bacterial membranes enhance the action of reactive oxygen species (ROS) produced by eumelanin degradation itself, also concurring with the final biocide action. These findings provide strategic information for the development of eumelanin-based systems with enhanced activity against drug-resistant strains

Dihydrophenanthrenes from a sicilian accession of himantoglossum robertianum (Loisel.) P. Delforge showed antioxidant, antimicrobial, and antiproliferative activities

The peculiar aspect that emerges from the study of Orchidaceae is the presence of various molecules, which are particularly interesting for pharmaceutical chemistry due to their wide range of biological resources. The aim of our study was to investigate the properties of two dihydrophenanthrenes, isolated, for the first time, from Himantoglossum robertianum (Loisel.) P. Delforge (Orchidaceae) bulbs and roots. Chemical and spectroscopic study of the bulbs and roots of Himantoglossum robertianum (Loisel.) P. Delforge resulted in the isolation of two known dihydrophenanthrenes—loroglossol and hircinol—never isolated from this plant species. The structures were evaluated based on1H-NMR,13C-NMR, and two-dimensional spectra, and by comparison with the literature. These two molecules have been tested for their possible antioxidant, antimicrobial, antiproliferative, and proapoptotic activities. In particular, it has been shown that these molecules cause an increase in the activity of superoxide dismutase (SOD), catalase (CAT), and glutathione S-transferase (GST) in polymorphonuclear leukocytes (PMN); show antimicrobial activity against Escherichia coli and Staphylococcus aureus, and have anti-proliferative effects on gastric cancer cell lines, inducing apoptosis effects. Therefore, these two molecules could be considered promising candidates for pharmaceutical and nutraceutical preparations

Environment‐sensitive fluorescent labelling of peptides by luciferin analogues

Environment‐sensitive fluorophores are very valuable tools in the study of molecular and cellular processes. When used to label proteins and peptides, they allow for the monitoring of even small variations in the local microenvironment, thus acting as reporters of conformational variations and binding events. Luciferin and aminoluciferin, well known substrates of firefly luciferase, are environment‐sensitive fluorophores with unusual and still‐unexploited properties. Both fluorophores show strong solvatochromism. Moreover, luciferin fluorescence is influenced by pH and water abundance. These features allow to detect local variations of pH, solvent polarity and local water concentration, even when they occur simultaneously, by analyzing excitation and emission spectra. Here, we describe the characterization of (amino)luciferin‐labeled derivatives of four bioactive peptides: the antimicrobial peptides GKY20 and ApoBL, the antitumor peptide p53pAnt and the integrin‐binding peptide RGD. The two probes allowed for the study of the interaction of the peptides with model membranes, SDS micelles, lipopolysaccharide micelles and Escherichia coli cells. Kd values and binding stoichiometries for lipopolysaccharide were also determined. Aminoluciferin also proved to be very well‐suited to confocal laser scanning microscopy. Overall, the characterization of the labeled peptides demonstrates that luciferin and aminoluciferin are previously neglected environment‐sensitive labels with widespread potential applications in the study of proteins and peptides

A new Bacillus subtilis gene with homology to Escherichia coli prc

We report the cloning of a 2-kb PstI-BamHI fragment of Bacillus subtilis DNA carrying an open reading frame of 1398 bp, herein designated orfRM1. This orf was shown to be transcribed only during vegetative growth from a putative o(A)-specific promoter. The deduced amino acid sequence predicted a polypeptide of 51 kDa (466 aa), which shows significant percentage of identity with the Escherichia coli Prc protein. However no Prc-like phenotypes were observed in a B. subtilis orfRM1 deletion-insertion mutant

SDS-PAGE patterns of whole cell proteins of Streptococcus thermophilus: impact of strain, growth phase and adaptation and relationship with stress response

In previous studies we demonstrated that a relatively large diversity of stress response patterns (acid, osmotic, oxidative, heat) exists among Streptococcus thermophilus strains. Changes in protein expression, evaluated by SDS–PAGE in 4 wild strains (CNBL7035, TH681, Y3, Sfi39) and in three Sfi39 mutants in which hrcA, ctsR and rr01 genes were inactivated showed that significant variations of proteins involved in general stress response (GSR) occur as a function of growth phase, adaptation and inactivation of stress response regulators. In this work we re-evaluate the previous results comparing two unsupervised (Hierarchical Cluster Analysis, HCA, and Principal Component Analysis, PCA) and one supervised (Partial Least Square Regression, PLSR) statistical techniques for the ability to extract information from SDS–PAGE patterns of wild type and mutant strains of S. thermophilus and to uncover relationships between protein patterns and stress tolerance. HCA and PCA are two purely descriptive techniques. The HCA showed that SDS–PAGE is an efficient tool to differentiate strains but did not shed any light on the relationships between band intensity and strain, growth phase or adaptation treatment. PCA helped to identify group of bands which covaried with the stress input factors butalso not allow to find a relationship between protein expression and stress tolerance. The PLS regression, even with the limitations due to the data set used in this study, appears as an extremely promising tools for the identification of complex relationships between design and response variables in the analysis of SDS–PAGE patterns of whole cell proteins