Antifungal Activity of Diketopiperazines and Stilbenes Against Plant Pathogenic Fungi In Vitro

The present study aimed to investigate antifungal activity of a stilbene and diketopiperazine compounds against plant pathogenic fungi, including Phytophthora capsici, P. colocasiae, Botrytis cinerea and Colletotrichum gloeosporioides. Minimal inhibition concentrations (MIC) and minimal fungicidal concentrations (MFC) of stilbenes and diketopiperazines for each fungus were determined using microplate method. Best activity was recorded by stilbenes against P. capsici and P. colocasiae. All four test compounds were effective in inhibiting different stages of the life cycle of test fungi. Stilbenes were more effective than diketopiperazines in inhibiting mycelial growth and inhibiting different stages of the life cycle of P. capsici and P. colocasiae. Rupture of released zoospores induced by stilbenes was reduced by addition of 100 mM glucose. The effects of stilbenes on mycelial growth and zoospore release, but not zoospore rupture, were reduced largely when pH value was above 7. In addition, stilbenes were investigated for its antifungal stability against Phytophthora sp. The results showed that stilbenes maintained strong fungistatic activity over a wide pH range (pH 4–9) and temperature range (70–120 °C). The compound stilbenes exhibited strong and stable broad-spectrum antifungal activity, and had a significant fungicidal effect on fungal cells. Results from prebiocontrol evaluations performed to date are probably useful in the search for alternative approaches to controlling serious plant pathogens.     

A Supramolecular-Based Dual-Wavelength Phototherapeutic Agent with Broad-Spectrum Antimicrobial Activity Against Drug-Resistant Bacteria

With the ever-increasing threat posed by the multi-drug resistance of bacteria, the development of non-antibiotic agents for the broad-spectrum eradication of clinically prevalent superbugs remains a global challenge. Here, we demonstrate the simple supramolecular self-assembly of structurally defined graphene nanoribbons (GNRs) with a cationic porphyrin (Pp4N) to afford unique one-dimensional wire-like GNR superstructures coated with Pp4N nanoparticles. This Pp4N/GNR nanocomposite displays excellent dual-modal properties with significant reactive-oxygen-species (ROS) production (in photodynamic therapy) and temperature elevation (in photothermal therapy) upon light irradiation at 660 and 808 nm, respectively. This combined approach proved synergistic, providing an impressive antimicrobial effect that led to the complete annihilation of a wide spectrum of Gram-positive, Gram-negative, and drug-resistant bacteria both in vitro and in vivo. The study also unveils the promise of GNRs as a new platform to develop dual-modal antimicrobial agents that are able to overcome antibiotic resistance.     

Turning on the Antimicrobial Activity of Gold Nanoclusters Against Multidrug-Resistant Bacteria**

In this work, we show that the addition of thiourea (TU) initiated broad-spectrum antimicrobial activity of otherwise inactive D-maltose-capped gold nanoclusters (AuNC-Mal). For example, AuNC-Mal/TU was effective against multidrug-resistant Pseudomonas aeruginosa with a minimum inhibitory concentration (MIC) of 1 μg mL⁻¹ (2.5 μM [Au]) while having 30–60 times lower in vitro cytotoxicity against mammalian cells. The reaction of AuNC-Mal and TU generated the antimicrobial species of [Au(TU)₂]⁺ and smaller AuNCs. TU increased the accumulation of Au in bacteria and helped maintain the oxidation state as Au^I (vs. Au^III). The modes of action included the inhibition of thioredoxin reductase, interference with the Cu^I regulation and depletion of ATP. Moreover, the antimicrobial activity did not change in the presence of colistin or carbonyl cyanide 3-chlorophenylhydrazone, suggesting that AuNC-Mal/TU was indifferent to the outer membrane barrier and to bacterial efflux pumps.     

Synergistic Antibacterial and Antibiofilm Effect Between (+)-Medioresinol and Antibiotics In Vitro

In this study, antibacterial effects of (+)-Medioresinol isolated from stem bark of Sambucus williamsii and its synergistic activities in combination with antibiotics such as ampicillin, cefotaxime, and chloramphenicol were tested by antibacterial susceptibility testing and checkerboard assay. (+)-Medioresinol possessed antibacterial effects against antibiotics-susceptible- or antibiotics-resistant strains. Most of combinations between (+)-Medioresinol and each antibiotic showed synergistic interaction (fractional inhibitory concentration index ≤0.5) against bacterial strains including antibiotics-resistant Pseudomonas aeruginosa. Furthermore, the antibiofilm effect of (+)-Medioresinol alone or in combination with each antibiotic was investigated. The results indicated that not only (+)-Medioresinol but also its combination with each antibiotic had antibiofilm activities. It concludes that (+)-Medioresinol has potential as a therapeutic agent and adjuvant for treatment of bacterial infection.     

Lobularia libyca: Phytochemical Profiling,Antioxidant and Antimicrobial Activity Using In Vitro and In Silico Studies

Lobularia libyca (L. libyca) is a traditional plant that is popular for its richness in phenolic compounds and flavonoids. The aim of this study was to comprehensively investigate the phytochemical profile by liquid chromatography, electrospray ionization and tandem mass spectrometry (LC-ESI-MS), the mineral contents and the biological properties of L. libyca methanol extract. L. libyca contains significant amounts of phenolic compounds and flavonoids. Thirteen compounds classified as flavonoids were identified. L. libyca is rich in nutrients such as Na, Fe and Ca. Moreover, the methanol extract of L. libyca showed significant antioxidant activity without cytotoxic activity on HCT116 cells (human colon cancer cell line) and HepG2 cells (human hepatoma), showing an inhibition zone of 13 mm in diameter. In silico studies showed that decanoic acid ethyl ester exhibited the best fit in β-lactamase and DNA gyrase active sites; meanwhile, oleic acid showed the best fit in reductase binding sites. Thus, it can be concluded that L. libyca can serve as a beneficial nutraceutical agent, owing to its significant antioxidant and antibacterial potential and due to its richness in iron, calcium and potassium, which are essential for maintaining a healthy lifestyle.     

Solvent-Free Synthesis of Nitrilotriacetamide and Diketopiperazines from Nitrilotriacetic Acid under Microwave Irradiation and Their Antimicrobial Activity

Efficient synthesis of dioxopiperazines‐diketopiperzines (DKPs)‐ and amide from nitrilotriacetic acid (NTA) using microwave irradiation and classical heating were described. All compounds were characterized using ¹H NMR, ¹³C NMR and elemental analysis. Antimicrobial effects of these compounds are also investigated. All tested compounds showed moderate antimicrobial activity.     

Synergistic Anticancer Effect of a Combination of Paclitaxel and 5-Demethylnobiletin Against Lung Cancer Cell Line In Vitro and In Vivo

Applied Biochemistry and Biotechnology - Lung cancer remains a highly prevalent disease and a leading cause of cancer-related deaths worldwide. Currently, exploring antitumor drugs derived from...     

Antimicrobial Activity of Dihydroisocoumarin Isolated from Wadi Lajab Sediment-Derived Fungus Penicillium chrysogenum: In Vitro and In Silico Study

Antibiotic resistance is considered a major health concern globally. It is a fact that the clinical need for new antibiotics was not achieved until now. One of the most commonly prescribed classes of antibiotics is β-Lactam antibiotics. However, most bacteria have developed resistance against β-Lactams by producing enzymes β-Lactamase or penicillinase. The discovery of new β-Lactamase inhibitors as new antibiotics or antibiotic adjuvants is essential to avoid future catastrophic pandemics. In this study, five dihydroisocoumarin: 6-methoxy mellein (1); 5,6-dihydroxymellein (2); 6-hydroxymellein (3); 4-chloro-6-hydroxymellein (4) and 4-chloro-5,6-di-hydroxymellein (5) were isolated from Wadi Lajab sediment-derived fungus Penicillium chrysogenum, located 15 km northwest of Jazan, KSA. The elucidation of the chemical structures of the isolated compounds was performed by analysis of their NMR, MS. Compounds 1–5 were tested for antibacterial activities against Gram-positive and Gram-negative bacteria. All of the compounds exhibited selective antibacterial activity against Gram-positive bacteria Staphylococcus aureus and Bacillus licheniformis except compound 3. The chloro-dihydroisocoumarin derivative, compound 4, showed potential antimicrobial activities against all of the tested strains with the MIC value between 0.8–5.3 μg/mL followed by compound 5, which exhibited a moderate inhibitory effect. Molecular docking data showed good affinity with the isolated compounds to β-Lactamase enzymes of bacteria; NDM-1, CTX-M, OXA-48. This work provides an effective strategy for compounds to inhibit bacterial growth or overcome bacterial resistance.     

Synthesis and in Vitro Evaluation of New Cephalosporins Exhibiting Antimicrobial Activity against Gram-Positive Bacteria,in Particular Methicillin-Resistant Staphylococci

The preparation and biological evaluation of 7β-[[2-(phenyl)thiazol-4-yl]acetamido]cephalosporins and 7β-[[(2-(pyridin-2-yl)thiazol-4-yl]acetamido]cephalosporins, 9a-o , substituted at the 3-position with acetyloxymethyl, chlorine, hydrogen, and methyl are described. Hantzsch's thiazole synthesis is employed to provide thiazoleacetic acids 5a-e , subsequently followed by Morpho CDI-assisted amidation to complete the synthesis of target cephalosporins 9a-o . These compounds display activity selectively against Gram-positive bacteria, but are inactive against most Gram-negative bacteria tested. Those with acetyloxymethyl at the 3-position, i.e., 9a, 9e, 9i, 9m , and 90 , exhibit activity with minimal inhibitory concentrations of 16 (μg/mL or lower against four strains of methicillin-resistant staphylococci, namely Staphylococcus aureus X400 and S13E and Staphylococcus epidermidis 270 and 222. Notably, 9a displays an activity profile similar to that of vancomycin regarding its spectrum and potency.     

Synthesis,Characterization, and In Vitro Antimicrobial Activity of Methyleneamine‐Linked Bis‐heterocycles

A new class of methyleneamine‐linked bis‐heterocycles that exhibit antimicrobial activity was synthesized. Bromination of 1 followed by condensation with thiourea gave 3 . The reaction of 3 with propargyl bromide in dry toluene under inert atmosphere led to the formation of 4 . Its subsequent reaction with different nitrile oxides using CuSO₄.5H₂O–sodiumascorbate system in a 2:1 mixture of water and tert‐butyl alcohol yielded the title compounds 6a , 6b , 6c , 6d , 6e , 6f , 6g , 6h , 6i , 6j , 6k , 6l in good yields. The identities of these compounds were confirmed following elemental analysis, IR, ¹H, ¹³C NMR, and mass spectral studies. All the title compounds exhibited pronounced in vitro antibacterial and antifungal activities.     

Novel Thiadiazole-Based Molecules as Promising Inhibitors of Black Fungi and Pathogenic Bacteria: In Vitro Antimicrobial Evaluation and Molecular Docking Studies

Novel 1,3,4-thiadiazole derivatives were synthesized through the reaction of methyl 2-(4-hydroxy-3-methoxybenzylidene) hydrazine-1-carbodithioate and the appropriate hydrazonoyl halides in the presence of a few drops of diisopropylethylamine. The chemical structure of the newly fabricated compounds was inferred from their microanalytical and spectral data. With the increase in microbial diseases, fungi remain a devastating threat to human health because of the resistance of microorganisms to antifungal drugs. COVID-19-associated pulmonary aspergillosis (CAPA) and COVID-19-associated mucormycosis (CAM) have higher mortality rates in many populations. The present study aimed to find new antifungal agents using the disc diffusion method, and minimal inhibitory concentration (MIC) values were estimated by the microdilution assay. An in vitro experiment of six synthesized chemical compounds exhibited antifungal activity against Rhizopus oryzae; compounds with an imidazole moiety, such as the compound 7, were documented to have energetic antibacterial, antifungal properties. As a result of these findings, this research suggests that the synthesized compounds could be an excellent choice for controlling black fungus diseases. Furthermore, a molecular docking study was achieved on the synthesized compounds, of which compounds 2, 6, and 7 showed the best interactions with the selected protein targets.     

Bioprospecting the Antibiofilm and Antimicrobial Activity of Soil and Insect Gut Bacteria

Antimicrobial resistance is a growing concern in public health and current research shows an important role for bacterial biofilms in recurrent or chronic infections. New strategies, therefore, are necessary to overcome antimicrobial resistance, through the development of new therapies that could alter or inhibit biofilm formation. In this sense, antibiofilm natural products are very promising. In this work, a bioprospection of antimicrobial and antibiofilm extracts from Uruguayan soil bacteria and insect gut bacteria was carried out. Extracts from extracellular broths were tested for their ability to inhibit planktonic cell growth and biofilm formation. Genomic analysis of Bacillus cereus ILBB55 was carried out. All extracts were able to inhibit the growth of, at least, one microorganism and several extracts showed MICs lower than 500 µg mL⁻¹ against microorganisms of clinical relevance (Staphylococcus aureus, Pseudomonas aeruginosa, and Enterobacter cloacae). Among the extracts evaluated for biofilm inhibition only ILBB55, from B. cereus, was able to inhibit, S. aureus (99%) and P. aeruginosa (62%) biofilms. Genomic analysis of this strain showed gene clusters similar to other clusters that code for known antimicrobial compounds. Our study revealed that extracts from soil bacteria and insect gut bacteria, especially from B. cereus ILBB55, could be potential candidates for drug discovery to treat infectious diseases and inhibit S. aureus and P. aeruginosa biofilms.     

In Vitro Photodynamic Activity of 5,15-bis(3-Hydroxyphenyl)porphyrin and Its Halogenated Derivatives Against Cancer Cells

5,15-Diarylporphyrins ( 1-5 ) with hydroxyl groups and halogens as substituents were prepared by condensation between unsubstituted dipyrromethane and halogenated m -hydroxybenzaldehydes. Photophysical properties show that the nonhalogenated porphyrin 1 has higher fluorescence yield but lower singlet oxygen formation quantum yield than the halogenated derivatives due to the heavy atom effect. The in vitro activity of these derivatives was tested against WiDr colorectal adenocarcinoma and A375 melanoma cancer cells. All porphyrins present a much higher phototoxicity than Photofrin^® with IC ₅₀ values lower than the 50 n m level for WiDr cells and 25 n m level for A375 cancer cells. The most photoactive compound is the nonhalogenated porphyrin 1 which also presents the highest uptake. Halogenated derivatives present much lower uptakes than 1 . However, their photoactivity is similar to compound 1 showing that their intrinsic photoactivity (ISP) is very high. Iodinated compound 4 presents the highest ISP. The greater ability of these porphyrins to destroy cancer cells could be related to their photophysical and photochemical properties.     

Aqueous Synthesis of Triphenylphosphine-Modified Gold Nanoparticles for Synergistic In Vitro and In Vivo Photothermal Chemotherapy

Triphenylphosphine (TPP) surface-functionalized and F-108 Pluronic-stabilized gold nanoparticles (F-108@TPP-AuNPs) have been synthesized through a one-step approach, leading to well-defined (9.6±1.6 nm) and water-soluble nanoparticles by microwave heating an aqueous solution of TPP-Au^ICl in the presence of a Pluronic polymer under basic conditions. TPP release was negligible under physiological conditions, but enhanced significantly at an acidic pH (5.4) mimicking that of a cancer cell. Laser irradiation (532 nm) raised the temperature of an aqueous solution of F-108@TPP-AuNPs to 51.7 °C within 5 min, confirming efficient light-to-heat conversion capabilities without significant photodegradation. TEM confirmed intracellular localization of F-108@TPP-AuNPs in the cytosol, endosomes and lysosomes of HeLa cells. F-108@TPP-AuNPs were well tolerated by HeLa cells and zebrafish embryos at ambient temperatures and became toxic upon heat activation, suggesting synergistic interactions between heat and cytotoxic action by TPP.     

Engineered Cyclotides with Potent Broad in Vitro and in Vivo Antimicrobial Activity

The search for novel antimicrobial agents to combat microbial pathogens is intensifying in response to the rapid development of drug resistance to current antibiotic therapeutics. Respiratory failure and septicemia are the leading causes of mortality among hospitalized patients. Here, the development of a novel engineered cyclotide with effective broad-spectrum antibacterial activity against several ESKAPE bacterial strains and clinical isolates is reported. The most active antibacterial cyclotide was extremely stable in serum, showed little hemolytic activity, and provided protection in vivo in a murine model of P. aeruginosa peritonitis. These results highlight the potential of the cyclotide scaffold for the development of novel antimicrobial therapeutic leads for the treatment of bacteremia.     

Antifungal Activity of Alpha-Mangostin against Colletotrichum gloeosporioides In Vitro and In Vivo

We investigated alpha-mangostin (α-mangostin, α-MG), a xanthone natural product extracted from the pericarp of mangosteen (Garcinia mangostana), for its antifungal activities and possible mechanism against Colletotrichum gloeosporioides, which causes mango anthracnose. The results demonstrated that α-MG had a relatively high in vitro inhibitory activity against C. gloeosporioides among 20 plant pathogenic fungi. The median effective concentration (EC₅₀) values of α-MG against mycelial growth were nearly 10 times higher than those of spore germination inhibition for both strains of C. gloeosporioides, the carbendazim-sensitive (CBD-s) and carbendazim-resistant (CBD-r). The results suggested that α-MG exhibited a better inhibitory effect on spore germination than on the mycelial growth of C. gloeosporioides. Further investigation indicated that the protective effect could be superior to the therapeutic effect for mango leaves for scab development. The morphological observations of mycelium showed that α-MG caused the accumulation of dense bodies. Ultrastructural observation further revealed that α-MG caused a decrease in the quantity and shape of the swelling of mitochondria in the mycelium cells of C. gloeosporioides. In addition, bioassays disclosed that the inhibitory activity of α-MG on spore germination was reduced by adding exogenous adenosine triphosphate (ATP). These results suggested that the mode of action of α-MG could be involved in the destruction of mitochondrial energy metabolism. The current study supports α-MG as a natural antifungal agent in crop protection.     

In Vitro Human Skin Penetration,Antioxidant and Antimicrobial Activity of Ethanol-Water Extract of Fireweed (Epilobium angustifolium L.)

Epilobium angustifolium L. is applied as an antiseptic agent in the treatment of skin diseases. However, there is a lack of information on human skin penetration of active ingredients with antioxidative potential. It seems crucial because bacterial infections of skin and subcutaneous tissue are common and partly depend on oxidative stress. Therefore, we evaluated in vitro human skin penetration of fireweed ethanol-water extracts (FEEs) by determining antioxidant activity of these extracts before and after penetration study using 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), and Folin–Ciocalteu methods. Microbiological tests of extracts were done. The qualitative and quantitative evaluation was performed using gas chromatography-mass spectrometry (GC-MS) and high-performance liquid chromatography (HPLC-UV) methods. The in vitro human skin penetration using the Franz diffusion chamber was assessed. The high antioxidant activity of FEEs was found. Gallic acid (GA), chlorogenic acid (ChA), 3,4-dihydroxybenzoic acid (3,4-DHB), 4-hydroxybenzoic acid (4-HB), and caffeic acid (CA) were identified in the extracts. The antibacterial activities were found against Serratia lutea, S. marcescens, Bacillus subtilis, B. pseudomycoides, and B. thuringiensis and next Enterococcus faecalis, E. faecium, Streptococcus pneumoniae, Pseudomonas aeruginosa, and P. fluorescens strains. In vitro penetration studies showed the penetration of some phenolic acids and their accumulation in the skin. Our results confirm the importance of skin penetration studies to guarantee the efficacy of formulations containing E. angustifolium extracts.