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Molecules (Basel, Switzerland) Jun 2024A new series of chiral 4,5-dihydro-1-[1,2,4]-triazoline molecules, featuring a β-ᴅ-glucopyranoside appendage, were synthesized via a 1,3-dipolar cycloaddition...
Stereoselective Asymmetric Syntheses of Molecules with a 4,5-Dihydro-1-[1,2,4]-Triazoline Core Possessing an Acetylated Carbohydrate Appendage: Crystal Structure, Spectroscopy, and Pharmacology.
A new series of chiral 4,5-dihydro-1-[1,2,4]-triazoline molecules, featuring a β-ᴅ-glucopyranoside appendage, were synthesized via a 1,3-dipolar cycloaddition reaction between various hydrazonyl chlorides and carbohydrate Schiff bases. The isolated enantiopure triazolines (-) were identified through high-resolution mass spectrometry (HRMS) and vibrational spectroscopy. Subsequently, their solution structures were elucidated through NMR spectroscopic techniques. Single-crystal X-ray analysis of derivative provided definitive evidence for the 3-D structure of this compound and revealed important intermolecular forces in the crystal lattice. Moreover, it confirmed the ()-configuration at the newly generated stereo-center. Selected target compounds were investigated for anti-tumor activity in 60 cancer cell lines, with derivative showing the highest potency, particularly against leukemia. Additionally, substituent-dependent anti-fungal and anti-bacterial behavior was observed.
Topics: Humans; Crystallography, X-Ray; Triazoles; Cell Line, Tumor; Antineoplastic Agents; Carbohydrates; Molecular Structure; Stereoisomerism; Acetylation; Structure-Activity Relationship; Magnetic Resonance Spectroscopy
PubMed: 38930904
DOI: 10.3390/molecules29122839 -
Molecules (Basel, Switzerland) Jun 2024The Lamiaceae family, which includes several well-known aromatic plants, is scientifically relevant due to its essential oils (EOs). In this work, four EOs from...
The Lamiaceae family, which includes several well-known aromatic plants, is scientifically relevant due to its essential oils (EOs). In this work, four EOs from Mediterranean species, namely L., L., L., and L., were evaluated for their volatile profiles and the biological activity in vitro to assess their potential use in the food and cosmetic sector. GC/MS analysis revealed dominant compounds, such as carvacrol, thymol, and eucalyptol. Regarding biological action, the samples exhibited antioxidant, cytotoxic, anti-inflammatory, antimicrobial, and antifungal activities, with and standing out. showed the lowest EC in the reducing power assay, and had the lowest EC in the DPPH assay. Most EOs also displayed excellent anti-inflammatory responses and antifungal properties, with and also demonstrating antibacterial activity. All EOs from Mediterranean species showed cytotoxicity against tumoral cell lines. Overall, the selected EOs stood out for their interesting bioactivities, with the obtained results underscoring their potential as natural preservatives and bioactive agents in various industrial applications, including food, pharmaceuticals, and cosmetics.
Topics: Oils, Volatile; Lamiaceae; Antioxidants; Humans; Anti-Inflammatory Agents; Gas Chromatography-Mass Spectrometry; Origanum; Salvia officinalis; Cell Line, Tumor; Thymus Plant; Anti-Infective Agents; Plants, Edible; Plant Oils; Thymol; Microbial Sensitivity Tests; Cymenes
PubMed: 38930892
DOI: 10.3390/molecules29122827 -
Molecules (Basel, Switzerland) Jun 2024The aim of this study was to obtain new halolactones with a gem-dimethyl group in the cyclohexane ring (at the C-3 or C-5 carbon) and a methyl group in the lactone ring...
The aim of this study was to obtain new halolactones with a gem-dimethyl group in the cyclohexane ring (at the C-3 or C-5 carbon) and a methyl group in the lactone ring and then subject them to biotransformations using filamentous fungi. Halolactones in the form of mixtures of two diasteroisomers were subjected to screening biotransformations, which showed that only compounds with a gem-dimethyl group located at the C-5 carbon were transformed. Strains from the genus carried out hydrolytic dehalogenation, while strains from the genus carried out hydroxylation of the C-7 carbon. Both substrates and biotransformation products were then tested for antimicrobial activity against multidrug-resistant strains of both bacteria and yeast-like fungi. The highest antifungal activity against and strains was obtained for compound , while antimicrobial activity against MRSA was obtained for compound .
Topics: Lactones; Anti-Bacterial Agents; Biotransformation; Microbial Sensitivity Tests; Fusarium; Antifungal Agents; Absidia; Molecular Structure; Candida albicans; Methicillin-Resistant Staphylococcus aureus
PubMed: 38930886
DOI: 10.3390/molecules29122820 -
Molecules (Basel, Switzerland) Jun 2024Cyclophilin A (CypA), the cellular receptor of the immunosuppressant cyclosporin A (CsA), is an abundant cytosolic protein and is involved in a variety of diseases. For...
Cyclophilin A (CypA), the cellular receptor of the immunosuppressant cyclosporin A (CsA), is an abundant cytosolic protein and is involved in a variety of diseases. For example, CypA supports cancer proliferation and mediates viral infections, such as the human immunodeficiency virus 1 (HIV-1). Here, we present the design of PROTAC (proteolysis targeting chimera) compounds against CypA to induce its intracellular proteolysis and to investigate their effect on immune cells. Interestingly, upon connecting to E3 ligase ligands, both peptide-based low-affinity binders and CsA-based high-affinity binders can degrade CypA at nM concentration in HeLa cells and fibroblast cells. As the immunosuppressive effect of CsA is not directly associated with the binding of CsA to CypA but the inhibition of phosphatase calcineurin by the CypA:CsA complex, we investigated whether a CsA-based PROTAC compound could induce CypA degradation without affecting the activation of immune cells. P3, the most efficient PROTAC compound discovered from this study, could deplete CypA in lymphocytes without affecting cell proliferation and cytokine production. This work demonstrates the feasibility of the PROTAC approach in depleting the abundant cellular protein CypA at low drug dosage without affecting immune cells, allowing us to investigate the potential therapeutic effects associated with the endogenous protein in the future.
Topics: Humans; Cyclophilin A; Cyclosporine; Proteolysis; T-Lymphocytes; Lymphocyte Activation; HeLa Cells; Cell Proliferation; Immunosuppressive Agents; Proteolysis Targeting Chimera
PubMed: 38930843
DOI: 10.3390/molecules29122779 -
Molecules (Basel, Switzerland) Jun 2024The content of chemical constituents in leaf extracts correlates positively with biological activities. The experimental objective was to carry out the phytochemical...
The content of chemical constituents in leaf extracts correlates positively with biological activities. The experimental objective was to carry out the phytochemical screening and purification of the major polyphenols from the leaves of . In addition, the anti- activity of the hydroalcoholic extract, fraction, subfractions and polyphenols purified were evaluated. After partitioning of the extract with ethyl acetate, the fractions were chromatographed on Sephadex LH-20 gel followed by RP-flash chromatography and monitored by TLC and RP-HPLC. The samples were characterized by mass spectrometry (LC-ESI-QTOF-MS) and subjected to the microdilution method in 96-well plates against strains of , and . Myricitrin (93.89%; /; / 463.0876), gallic acid (99.9%; /; / 169.0142), and ellagic acid (94.2%; /; / 300.9988) were recovered. The polyphenolic fraction (62.67% (/) myricitrin) and the ellagic fraction (67.86% (/) ellagic acid) showed the best antifungal performance (MIC between 62.50 and 500 μg/mL), suggesting an association between the majority constituents and the antifungal response of derivatives. However, there is a clear dependence on the presence of the complex chemical mixture. In conclusion, chromatographic strategies were effectively employed to recover the major polyphenols from the leaves of the species.
Topics: Polyphenols; Eugenia; Plant Leaves; Antifungal Agents; Plant Extracts; Microbial Sensitivity Tests; Candida; Tandem Mass Spectrometry; Spectrometry, Mass, Electrospray Ionization; Chromatography, High Pressure Liquid; Gallic Acid
PubMed: 38930827
DOI: 10.3390/molecules29122761 -
Molecules (Basel, Switzerland) Jun 2024is a species of pharmacological interest for providing volatile and non-volatile extracts with antifungal and amebicidal properties. The biological activities of...
is a species of pharmacological interest for providing volatile and non-volatile extracts with antifungal and amebicidal properties. The biological activities of non-volatile extracts may be related to the presence of coumarins, a promising group of secondary metabolites. In the present study, leaves and inflorescences previously used for the extraction of essential oils instead of being disposed of were subjected to extraction with supercritical CO after pretreatment with microwaves. An experimental design was followed to seek the best extraction condition with the objective function being the maximum total extract. Pressure and temperature were statistically significant factors, and the optimal extraction condition was 240 bar, 60 °C, and pretreatment at 30 °C. The applied mathematical models showed good adherence to the experimental data. The extracts obtained by supercritical CO were analyzed and the presence of coumarins was confirmed. The extract investigated for cytotoxicity against bladder tumor cells (T24) exhibited significant reduction in cell viability at concentrations between 6 and 12 μg/mL. The introduction of green technology, supercritical extraction, in the exploration of as a source of coumarins represents a paradigm shift with regard to previous studies carried out with this species, which used organic solvents. Furthermore, the concept of circular bioeconomy was applied, i.e., the raw material used was the residue of a steam-distillation process. Therefore, the approach used here is in line with the sustainable exploitation of native plants to obtain extracts rich in coumarins with cytotoxic potential against cancer cells.
Topics: Coumarins; Carbon Dioxide; Plant Extracts; Humans; Chromatography, Supercritical Fluid; Plant Components, Aerial; Cell Line, Tumor; Cell Survival; Antineoplastic Agents, Phytogenic
PubMed: 38930806
DOI: 10.3390/molecules29122741 -
Microorganisms Jun 2024The anti-fungal properties of the probiotic bacterium have been studied extensively in agriculture and ecology, but their applications in the built environment remain...
The anti-fungal properties of the probiotic bacterium have been studied extensively in agriculture and ecology, but their applications in the built environment remain to be determined. Our work aims to utilize this biological component to introduce new diverse anti-mold properties into paint. "Mold" refers to the ubiquitous fungal species that generate visible multicellular filaments commonly found in household dust. The development of mold leads to severe health problems for occupants, including allergic response, hypersensitivity pneumonitis, and asthma, which have significant economic and clinical outcomes. We here demonstrate the robust effect of a commercial paint enhanced with Bacillus subtilis cells against the common mold agent, , and identify three biosynthetic clusters essential for this effect. Our results lay the foundation for bio-convergence and synthetic biology approaches to introduce renewable and environmentally friendly bio-anti-fungal agents into the built environment.
PubMed: 38930607
DOI: 10.3390/microorganisms12061226 -
Microorganisms Jun 2024The World Health Organization (WHO) has prioritized developing new drugs against specific bacteria and fungi, such as and spp. While is commonly called the...
The World Health Organization (WHO) has prioritized developing new drugs against specific bacteria and fungi, such as and spp. While is commonly called the "cure-everything", its scientifically proven benefits are limited to anti-inflammatory and antioxidant actions. Therefore, this study aims to determine the spectrum of antimicrobial activity of and assess its cytotoxicity. Thus, broth microdilution test was conducted according to the CLSI M7-A9 and M27-A3 reference methods. After screening, microbial species with minimum inhibitory concentration (MIC) values were selected for biofilm tests. These tests evaluated biomass using the crystal violet (CV) test, metabolic activity using the MTT assay, and structural analysis via Scanning Electron Microscopy (SEM). Cytotoxicity was evaluated in human gingival fibroblasts (FMM-1). There were reductions of 29.4 and 42.7% in CV and MTT assays for spp. biofilm. and biofilms showed a decrease of 15.7 and 28.6%, respectively. Cell viability tests indicated 55.1, 56.9, and 65.5% of viability after contact with 1.93, 0.96, and 0.48 mg/mL of the extract, respectively. The extract showed antimicrobial action, displayed MIC values, and antibiofilm action on , and . The cytotoxicity on the FMM-1 cell line was dose-dependent. Therefore, extract holds significant potential for developing new drugs.
PubMed: 38930547
DOI: 10.3390/microorganisms12061165 -
Microorganisms Jun 2024Licorice () is a plant of the genus Glycyrrhiza in the family / and is a renowned natural herb with a long history of medicinal use dating back to ancient times.... (Review)
Review
Licorice () is a plant of the genus Glycyrrhiza in the family / and is a renowned natural herb with a long history of medicinal use dating back to ancient times. Glycyrrhizin (GLY), the main active component of licorice, serves as a widely utilized therapeutic agent in clinical practice. GLY exhibits diverse medicinal properties, including anti-inflammatory, antibacterial, antiviral, antitumor, immunomodulatory, intestinal environment maintenance, and liver protection effects. However, current research primarily emphasizes GLY's antiviral activity, while providing limited insight into its antibacterial properties. GLY demonstrates a broad spectrum of antibacterial activity via inhibiting the growth of bacteria by targeting bacterial enzymes, impacting cell membrane formation, and altering membrane permeability. Moreover, GLY can also bolster host immunity by activating pertinent immune pathways, thereby enhancing pathogen clearance. This paper reviews GLY's inhibitory mechanisms against various pathogenic bacteria-induced pathological changes, its role as a high-mobility group box 1 inhibitor in immune regulation, and its efficacy in combating diseases caused by pathogenic bacteria. Furthermore, combining GLY with other antibiotics reduces the minimum inhibitory concentration, potentially aiding in the clinical development of combination therapies against drug-resistant bacteria. Sources of information were searched using PubMed, Web of Science, Science Direct, and GreenMedical for the keywords "licorice", "Glycyrrhizin", "antibacterial", "anti-inflammatory", "HMGB1", and combinations thereof, mainly from articles published from 1979 to 2024, with no language restrictions. Screening was carried out by one author and supplemented by others. Papers with experimental flaws in their experimental design and papers that did not meet expectations (antifungal papers, etc.) were excluded.
PubMed: 38930536
DOI: 10.3390/microorganisms12061155 -
Microorganisms May 2024and are extensively utilized to investigate fungal pathogenic mechanisms and to develop biological control agents. Notwithstanding, notable distinctions exist in their...
and are extensively utilized to investigate fungal pathogenic mechanisms and to develop biological control agents. Notwithstanding, notable distinctions exist in their pathogenicity against the same host insect. This study aimed to elucidate the pathogenic differences between and by examining the impact of various ratios of strain AJS91881 and strain SXBN200920 on fifth instar larvae of , focusing on early infection stages and intestinal microbial community structure. The lethal time 50 (LT) for was significantly lower than that for , indicating greater efficacy. Survival analyses in mixed groups (ratios of 1:9, 1:1, and 9:1 to ) consistently demonstrated higher virulence of . Intestinal microbial diversity analysis revealed a significant increase in and in larvae infected with , whereas was notably higher in those infected with Additionally, significant shifts in microbial genera abundances were observed across all mixed infection groups. KEGG pathway enrichment analysis indicated that and employ distinct pathogenic strategies during early infection stages. tests confirmed the superior growth and stress resistance of compared to but the antifungal ability of was better than that of In conclusion, our findings provide preliminary insights into the differential pathogenic behaviors of and during the early infection stages in larvae, enhancing our understanding of their mechanisms and informing biological pest control strategies in agriculture and forestry.
PubMed: 38930511
DOI: 10.3390/microorganisms12061129