A dendritic cell-recruiting, antimicrobial blood clot hydrogel for melanoma recurrence prevention and infected wound management.

Surgical resection, the mainstay for melanoma treatment, faces challenges due to high tumor recurrence rates and complex postoperative wound healing. Chronic inflammation from residual disease and the risk of secondary infections impede healing. We introduce an innovative, injectable hydrogel system that integrates a multifaceted therapeutic approach. The hydrogel, crosslinked by calcium ions with sodium alginate, encapsulates a blood clot rich in dendritic cells (DCs) chemoattractants and melanoma cell-derived nanovesicles (NVs), functioning as a potent immunostimulant. This in situ recruitment strategy overcomes the limitations of subcutaneous tumor vaccine injections and more effectively achieves antitumor immunity. Additionally, the hydrogel incorporates Chlorella extracts, enhancing its antimicrobial properties to prevent wound infections and promote healing. One of the key findings of our research is the dual functionality of Chlorella extracts; they not only expedite the healing process of infected wounds but also increase the hydrogel's ability to stimulate an antitumor immune response. Given the patient-specific nature of the blood clot and NVs, our hydrogel system offers customizable solutions for individual postoperative requirements. This personalized approach is highlighted by our study, which demonstrates the synergistic impact of the composite hydrogel on preventing melanoma recurrence and hastening wound healing, potentially transforming postsurgical melanoma management.

Recent approaches in the application of antimicrobial peptides in food preservation.

Antimicrobial peptides (AMPs) are small peptides existing in nature as an important part of the innate immune system in various organisms. Notably, the AMPs exhibit inhibitory effects against a wide spectrum of pathogens, showcasing potential applications in different fields such as food, agriculture, medicine. This review explores the application of AMPs in the food industry, emphasizing their crucial role in enhancing the safety and shelf life of food and how they offer a viable substitute for chemical preservatives with their biocompatible and natural attributes. It provides an overview of the recent advancements, ranging from conventional approaches of using natural AMPs derived from bacteria or other sources to the biocomputational design and usage of synthetic AMPs for food preservation. Recent innovations such as structural modifications of AMPs to improve safety and suitability as food preservatives have been discussed. Furthermore, the active packaging and creative fabrication strategies such as nano-formulation, biopolymeric peptides and casting films, for optimizing the efficacy and stability of these peptides in food systems are summarized. The overall focus is on the spectrum of applications, with special attention to potential challenges in the usage of AMPs in the food industry and strategies for their mitigation.

Endophytic fungal diversity and bioactive potentials: investigating antimicrobial and antioxidant activities.

This study investigates the colonization of endophytic fungi in nettle leaf tissues and evaluates their antibacterial and antioxidant activities. Using an inverted optical microscope, extensive fungal colonization was observed in all leaf parts, with hyphae prevalent in epidermal cells, parenchyma cells, and vascular tissues. 144 endophytic fungal isolates were isolated from 800 leaf fragments, indicating an 18% retention rate. ANOVA analysis revealed significant differences (p < 0. 001) in colonization frequencies among 20 subjects, with subject 3 showing the highest frequency (40%) and subject 11 the lowest (2. 5%). Ethyl acetate extracts of the three most abundant endophytic fungi demonstrated notable antibacterial activity against both Gram-positive and Gram-negative bacteria, including methicillin-resistant Staphylococcus aureus (MRSA). Inhibition zones ranged from 9. 5 to 15. 16 mm, with minimum inhibitory concentrations (MICs) between 0. 19 to 25 mg/mL. Alternaria sp. exhibited the highest antimicrobial activity against MRSA. Antioxidant activity was assessed using the DPPH radical scavenging test and FRAP method. All extracts showed substantial free radical scavenging properties, with IC50 values close to those of standards like BHT. Alternaria sp. had the highest antioxidant activity, followed by Epicocum sp. and Ulocladium sp. The FRAP method confirmed high reducing potential, with Alternaria sp. again exhibiting the highest activity. These findings highlight the potential of endophytic fungi in nettle leaves as sources of antimicrobial and antioxidant agents, with significant implications for pharmaceutical and biotechnological applications.

Bioactivity of Amphidinol-Containing Extracts of Amphidinium carterae Grown Under Varying Cultivation Conditions.

Microalgae are of great interest due to their ability to produce valuable compounds, such as pigments, omega-3 fatty acids, antioxidants, and antimicrobials. The dinoflagellate genus Amphidinium is particularly notable for its amphidinol-like compounds, which exhibit antibacterial and antifungal properties. This study utilized a two-stage cultivation method to grow Amphidinium carterae CCAP 1102/8 under varying conditions, such as blue LED light, increased salinity, and the addition of sodium carbonate or hydrogen peroxide. After cultivation, the biomass was extracted and fractionated using solid-phase extraction, yielding six fractions per treatment. These fractions were analyzed using Liquid Chromatography-High-Resolution Mass Spectrometry (LC-HRMS/MS) to identify their chemical components. Key amphidinol compounds (AM-B, AM-C, AM-22, and AM-A) were identified, with AM-B being the most abundant in Fraction 4, followed by AM-C. Fraction 5 also contained a significant amount of AM-C along with an unknown compound. Fraction 4 returned the highest antimicrobial activity against the pathogens Staphylococcus aureus, Enterococcus faecalis, and Candida albicans, with Minimal Biocidal Concentrations (MBCs) ranging from 1 to 512 µg/mL. Results indicate that the modulation of both amphidinol profile and fraction bioactivity can be induced by adjusting the cultivation parameters used to grow two-stage batch cultures of A. carterae.

An antimicrobial microneedle patch promotes functional healing of infected wounds through controlled release of adipose tissue-derived apoptotic vesicles.

The high incidence and mortality rates associated with acute and chronic wound infections impose a significant burden on global healthcare systems. In terms of the management of wound infection, the reconstruction and regeneration of skin appendages are essential for the recovery of mechanical strength and physiological function in the regenerated skin tissue. Novel therapeutic approaches are a requisite for enhancing the healing of infected wounds and promoting the regeneration of skin appendages. Herein, a novel antimicrobial microneedle patch has been fabricated for the transdermal controlled delivery of adipose tissue-derived apoptotic vesicles (ApoEVs-AT@MNP) for the treatment of infected wounds, which is expected to achieve high-quality scarless healing of the wound skin while inhibiting the bacteria in the infected wound. The microneedle patch (MNP) system possesses adequate mechanical strength to penetrate the skin, allowing the tips to remain inside tissue for continuous active release of biomolecules, and subsequently degrades safely within the host body. In vivo transplantation demonstrates that ApoEVs-AT@MNP not only inhibits bacterial proliferation in infected wounds but also significantly promotes effective and rapid scarless wound healing. Particularly noteworthy is the ability of ApoEVs-AT@MNP to promote the rapid formation of mature, evenly arranged hair follicles in infected wounds, observed as early as 8 days following implantation, which is essential for the restoration of skin function. This rapid development of skin appendages has not been reported this early in previous studies. Therefore, ApoEVs-AT@MNP has emerged as an excellent, painless, non-invasive, and highly promising treatment for infected wounds.

Antimicrobial hard denture reliners using quaternary ammonium methacryloxy silicate (K18 QAMS) and K18-functionalized filler.

OBJECTIVE: To determine the effects of adding a quaternary ammonium methacryloxy silicate (K18) and K18-functionalized filler (K18-Filler) on the material and antimicrobial properties of a hard denture reline material. MATERIALS AND METHODS: 30% K18 in methyl methacrylate (K18-MMA; 0-20 wt% of reliner) and K18-Filler (0-30 wt% of reliner) were incorporated into KoolinerTM hard denture reliner. KoolinerTM served as the control. The cure (Shore A hardness), hydrophilicity (contact angles), mechanical (3-point bend test), water sorption, and antimicrobial properties against Streptococcus mutans, S. sanguinis, and Candida albicans were determined. RESULTS: Most K18 groups cured well and had comparable Shore A hardness values (range ~52 to 70 DHN) to that of controls (67.2 ± 1.8 DHN; Bonferroni corrected p > 0.0003). Even the softest group had hardness values within the range of commercial products. Half of the K18 groups had comparable contact angles to that of controls (range ~75° to 80° vs 83.41° ± 2.66°; Bonferroni corrected p > 0.0003), and most were within the range of commercial liners. K18-MMA and K18-Filler increased modulus but decreased ultimate transverse strength (UTS). All experimental groups had comparable or higher moduli than controls (range ~966 to 2069 MPa vs 1340 ± 119 MPa; Bonferroni corrected p < 0.0003), but only half of the experimental groups had comparable UTS to that of controls (range ~41 to 49 MPa vs 55.8 ± 1.5 MPa; Bonferroni corrected p > 0.0003). The 15% and 20% K18-MMA with 30% K18-Filler groups had significant antimicrobial activity against all three microbes (p < 0.05). However, the 15% and 20% K18-MMA with 30% K18-Filler groups had significantly higher water sorption at early time points (p < 0.05). After 8 weeks, they were comparable to each other (p > 0.05). CONCLUSIONS: K18-MMA and K18-Filler are promising antimicrobial additives that produce hard denture liners with material properties within the range of commercial products and significant antimicrobial properties against S. mutans, S. sanguinis, and C. albicans. Further development is needed to reduce water sorption.

Characterization and applications of iron oxide nanoparticles synthesized from Phyllanthus emblica fruit extract.

Nanotechnology is a treasure trove of diversified themes which are endowed with broad applications. Herein, iron oxide (Fe2O3) nanoparticles were synthesized using Phyllanthus emblica aqueous fruit extract. The UV-Visible spectrum exhibited a surface plasmon resonance peak at 295nm. Fourier Transform Infrared Spectroscopy provided insight into the functional groups responsible for capping. X-ray diffraction analysis authenticated the crystalline nature of nanoparticles, while energy dispersive X-ray spectroscopy divulged that iron and oxygen comprised 54% of the nanoparticles' weight. Scanning electron microscopy established irregular morphology and agglomeration of nanoparticles. The Fe2O3 nanoparticles validated potent antimicrobial activity against 11 bacterial and 1 fungal isolates. The biggest zone of inhibition (23mm) was measured against S. enterica, whereas the smallest zone of inhibition (12mm) was documented against C. albicans and E. coli. The values for minimum inhibitory concentration ranged between 10 and 15µg/ml for all microbes. Nevertheless, no synergy was exhibited by the nanoparticles with any of the selected antibiotics (Fractional Inhibitory Concentration Index > 1). The photocatalytic dye degradation capability of Fe2O3 nanoparticles was assessed and the observations implied a significant increase in degradation of methyl red although, not of methylene blue. Furthermore, the nanoparticles were in possession of substantial antioxidant (34-38%) and anti-inflammatory (31-38%) capacities. Consequent upon the robust activities of P. emblica-mediated nanoparticles, these can be scrutinized for biomedical and environmental implementations in future.

Phyto-safe in vitro regeneration and harnessing antimicrobial-resistant endophytes as bioinoculants for enhanced growth and secondary metabolites yield in Nilgirianthus ciliatus.

Nilgirianthus ciliatus, extensively exploited for its pharmacological properties, is now classified as vulnerable. In vitro micropropagation offers a sustainable approach for ecological conservation and rational utilization of this biodiversity resource. This study aimed to reduce endophytes during in vitro propagation and isolating antimicrobial-resistant endophytes from N. ciliatus by employing various concentrations and exposure times of Plant Preservative Mixture (PPM). Optimal results were observed when nodal explants treated with 0.3% PPM for 8 h, followed by inoculation in Murashige and Skoog (MS) medium supplemented with 3 mg/L 6-benzylaminopurine (BAP) and 0.3% PPM. This protocol achieved 82% shoot regeneration with minimal endophytic contamination, suggesting that the duration of explant exposure to PPM significantly influences endophyte reduction. Two antimicrobial-resistant endophytes were isolated and identified as Bacillus cereus and Acinetobacter pittii through 16S rDNA sequencing. These endophytes exhibited plant growth-promoting characteristics, including amylolytic, proteolytic, lipolytic activities, indole-3-acetic acid production, phosphate solubilization, and stress tolerance. In vivo application of these endophytes as bioinoculants to N. ciliatus not only improved growth parameters but also significantly increased the levels of pharmacologically important compounds, squalene, and stigmasterol, as confirmed by High-performance thin-layer chromatography (HPTLC). This study demonstrates that PPM is a promising alternative for sustainable micropropagation of N. ciliatus. Furthermore, it highlights the potential of antimicrobial-resistant endophytes as bioinoculants to improve growth and medicinal value, offering a sustainable solution for conservation and large-scale cultivation of this species.

Reduction of bioburden on large area surfaces through use of a supplemental residual antimicrobial paint.

Paint is a versatile material that can be used to coat surfaces for which routine disinfection practices may be lacking. EPA-registered copper-containing supplemental residual antimicrobial paints could be used to reduce the bioburden on often-neglected surfaces. An interventional study was conducted by painting the walls of a preschool restroom and metal locker surfaces in two hospital locker rooms with a copper-containing antimicrobial paint to evaluate the potential for bioburden reduction compared to a non-copper-containing control paint. The antimicrobial paint reduced the bioburden on the preschool restroom walls by 57% and on lockers in one locker room by 63% compared to the control paint; no significant difference was observed between the two paint types in the second locker room. The upper quartile bacterial counts, which drive the overall risk by increasing exposure to pathogens, also exhibited 63% and 47% reductions for the antimicrobial paint compared to the control paint in the preschool restroom and the first locker room, respectively. Because detectible levels of bioburden are found on large-area surfaces such as walls and lockers, surfaces painted with copper-containing paints may make large-area surfaces that are prone to contamination safer in a way that is practical and economical.

Biological activities of derived pigments and polyphenols from the newly recorded alga Phyllymenia gibbesii.

The newly recorded Phyllymenia gibesii in the Mediterranean Sea at Alexandria coast of Egypt is regarded as a significant source of bioactive substances and is applied as an antioxidant, anti-inflammatory, and antimicrobial agent. According to the HPLC chromatograms, the acetone extract of P. gibesii comprised ten photosynthetic pigments (chlorophyll-a, chlorophyll-d, α-carotene, ß-carotene, phycocyanin, allophycocyanin, antheraxanthin, ß-cryptoxanthin, lutein, and violaxanthin). Total carotenoids were the dominant class in the pigments' profile, achieving a concentration of 257 g/g dry weight. The P. gibbesii extract had a total content of phenols (146.67 mg/g) and a total content of flavonoids (104.40 mg/g). The capacity of all the investigated biological activities augmented with the concentration of the algal extract. The maximal DPPH scavenging capacity was 81.44%, with an inhibitory concentration (IC50) of 9.88 µg/mL. Additionally, the highest ABTS scavenging capacity was 89.62%, recording an IC50 of 21.77 µg/mL. The hemolytic activity of P. gibbesii attained a maximum capacity of 49.88% with an IC50 of 100.25 µg/mL. Data also showed the maximum anti-inflammatory effectiveness at 81.25%, with an IC50 of 99.75 µg/mL. Furthermore, the extract exhibited antimicrobial capacity against all reference strains, particularly at high concentrations (0.1 mg/mL), with the greatest effect on C. albicans and E. coli.

Entrapment of antimicrobial compounds in a metal matrix for crop protection.

Agricultural yields are often limited by damage caused by pathogenic microorganisms, including plant-pathogenic bacteria. The chemical control options to cope with bacterial diseases in agriculture are limited, predominantly relying on copper-based products. These compounds, however, possess limited efficacy. Therefore, there is an urgent need to develop novel technologies to manage bacterial plant diseases and reduce food loss. In this study, a new antimicrobial agent was developed using a doping method that entraps small bioactive organic molecules inside copper as the metal matrix. The food preservative agent lauroyl arginate ethyl ester (ethyl lauroyl arginate; LAE) was chosen as the doped organic compound. The new composites were termed LAE@[Cu]. Bactericidal assays against Acidovorax citrulli, a severe plant pathogen, revealed that LAE and copper in the composites possess a synergistic interaction as compared with each component individually. LAE@[Cu] composites were further characterised in terms of chemical properties and in planta assays demonstrated their potential for further development as crop protection agents.

Highly Specific Polyphenolic Colloids as Alternatives to Antimicrobials in Livestock Production.

The dispersion of antibiotics in livestock farming represents a health concern worldwide, contributing to the spread of antimicrobial-resistant bacteria through animals, the environment, and humans. Phenolic compounds could be alternatives to antibiotics, once drawbacks such as their low water solubility, bioavailability, and reduced stability are overcome. Although nano- or micro-sized formulations could counter these shortcomings, they do not represent cost-effective options. In this study, three phenolic compounds, obtained from wood-processing manufacturers, were characterized, revealing suitable features such as their antioxidant activity, size, and chemical and colloidal stability for in-field applications. The minimum inhibitory concentration (MIC) of these colloidal suspensions was measured against six bacterial strains isolated from livestock. These particles showed different inhibition behaviors: Colloidal chestnut was effective against one of the most threatening antibiotic-resistant pathogens, i.e., S. aureus, but ineffective toward E. coli. Instead, colloidal pine showed a weak effect on S. aureus but specificity toward E. coli. The present proof-of-concept points at colloidal polyphenols as valuable alternatives for antimicrobial substitutes in the livestock context.

Preliminary In Vitro Evaluation of Silver, Copper and Gold Nanoparticles as New Antimicrobials for Pathogens That Induce Bovine Locomotion Disorders.

Lameness is a crucial problem in dairy farming. It worsens the welfare of cattle, reduces the milk yield, and causes economic losses. The etiology of lameness is varied and the cattle's condition may be infectious or non-infectious. The aim of this research was to analyze the biocidal properties of silver (AgNPs), gold (AuNPs), and copper (CuNPs) nanoparticles against bacteria causing lameness in cattle. The isolated pathogens used were Aerococcus viridans, Corynebacterium freneyi, Corynebacterium xerosis, and Trueperella pyogenes. The tested concentrations of nanoparticles were 50, 25, 12.5, 6.25, 3.125, and 1.56 mg/L. The methods used included the isolation of pathogens using standard microbiological procedures and their identification using mass spectrometry, physicochemical analysis, transmission electron microscopy, and cytotoxicity tests. Studies have shown that AgNPs at 3.125 and 1.56 mg/L concentrations, and CuNPs at 25 and 12.5 mg/L concentrations, have strong biocidal properties, while AuNPs have the weakest antimicrobial properties. The very limited number of in vivo studies focusing on lameness prevention in cattle indicate that new solutions need to be developed. However, further studies are necessary to evaluate if nanoparticles (NPs) may, in the future, become components of innovative biocides used to prevent lameness in dairy cattle.

The Archetypal Gamma-Core Motif of Antimicrobial Cys-Rich Peptides Inhibits H+-ATPases in Target Pathogens.

Human lactoferrin (hLf) is an innate host defense protein that inhibits microbial H+-ATPases. This protein includes an ancestral structural motif (i.e., γ-core motif) intimately associated with the antimicrobial activity of many natural Cys-rich peptides. Peptides containing a complete γ-core motif from hLf or other phylogenetically diverse antimicrobial peptides (i.e., afnA, SolyC, PA1b, PvD1, thanatin) showed microbicidal activity with similar features to those previously reported for hLf and defensins. Common mechanistic characteristics included (1) cell death independent of plasma membrane (PM) lysis, (2) loss of intracellular K+ (mediated by Tok1p K+ channels in yeast), (3) inhibition of microbicidal activity by high extracellular K+, (4) influence of cellular respiration on microbicidal activity, (5) involvement of mitochondrial ATP synthase in yeast cell death processes, and (6) increment of intracellular ATP. Similar features were also observed with the BM2 peptide, a fungal PM H+-ATPase inhibitor. Collectively, these findings suggest host defense peptides containing a homologous γ-core motif inhibit PM H+-ATPases. Based on this discovery, we propose that the γ-core motif is an archetypal effector involved in the inhibition of PM H+-ATPases across kingdoms of life and contributes to the in vitro microbicidal activity of Cys-rich antimicrobial peptides.

Antimicrobial Activity of Chalcones with a Chlorine Atom and Their Glycosides.

Chalcones, secondary plant metabolites, exhibit various biological properties. The introduction of a chlorine and a glucosyl substituent to the chalcone could enhance its bioactivity and bioavailability. Such compounds can be obtained through a combination of chemical and biotechnological methods. Therefore, 4-chloro-2'-hydroxychalcone and 5'-chloro-2'-hydroxychalcone were obtained by synthesis and then glycosylated in two filamentous fungi strains cultures, i.e., Isaria fumosorosea KCH J2 and Beauveria bassiana KCH J1.5. The main site of the glycosylation of both compounds by I. fumosorosea KCH J2 was C-2' and C-3 when the second strain was utilized. The pharmacokinetics of these compounds were predicted using chemoinformatics tools. Furthermore, antimicrobial activity tests were performed. Compounds significantly inhibited the growth of the bacteria strains Escherichia coli 10536, Staphylococcus aureus DSM 799, and yeast Candida albicans DSM 1386. Nevertheless, the bacterial strain Pseudomonas aeruginosa DSM 939 exhibited significant resistance to their effects. The growth of lactic acid bacteria strain Lactococcus acidophilus KBiMZ 01 bacteria was moderately inhibited, but strains Lactococcus rhamnosus GG and Streptococcus thermophilus KBM-1 were completely inhibited. In summary, chalcones substituted with a chlorine demonstrated greater efficacy in inhibiting the microbial strains under examination compared to 2'-hydroxychalcone, while aglycones and their glycosides exhibited similar effectiveness.

Exploring the Bioactive Potential of Moroccan Lemon Grass (Cymbopogon citratus L.): Investigations on Molecular Weight Distribution and Antioxidant and Antimicrobial Potentials.

Research on lemon grass (Cymbopogon citratus L.) revealed a variety of active molecules and examined their biological characteristics. However, most of these studies were conducted on wild varieties, while cultivated plants were addressed less. This study aimed to characterize the biomolecules and biological activities of lemon grass growing under North African conditions in Morocco. Phenolic compound profiles of aqueous (AE), ethanol (EE), and methanol (ME) extracts and their fractions were obtained with steric exclusion chromatography on Sephadex G50 gel and identified by LC-MS/MS. Then, total polyphenols (TPC), flavonoids (TFC), and antioxidant activities (FRAP: scavenging value and TAC: Total Antioxidant Capacity) of the fraction were evaluated, as well as the antimicrobial activity. The obtained results showed that the ME contained eight major compounds (i.e., apigenine-7-O-rutinoside and myricitine-3-O-rutinoside). The AE showed the presence of five molecules (i.e., kaempferol-3-O-glucuronide), while EE showed the presence of three molecules (i.e., quercetine-3-O-rutinoside). Regarding the chemical characterization, the highest value of total phenolic content (TPC) was obtained in AE (25) (4.60 ± 0.29 mg/g), and the highest value of total flavonoid content (TFC) was obtained in ME (29) (0.7 ± 0.08 mg/g). Concerning the antioxidant activity, the highest FRAP was obtained in ME (29) (97.89%), and the highest total antioxidant capacity (TAC) was obtained in ME (29) (89.89%). Correlation between FRAP, TPC, and TFC was noted only in fractions of AE and ME. All tested extracts of C. citratus and their fractions showed a significant antimicrobial effect. The lowest minimum inhibitory concentration (MIC) was recorded for ME against E. coli. Extracts' biological activities and their fractions were governed by their active molecules. These data are new and clarify a novel aspect of bioactive molecules in the extracts of cultivated C. citratus. Equally, throughout this research, we clarified the relationship between identified molecules and their biological properties, including antioxidant and anti-microbial activities, which is new for the study area. This study is suggested as a reference for comparative studies and other assays of other biological activities for the study plant.

Design, Synthesis, and Antimicrobial Activity of Amide Derivatives Containing Cyclopropane.

As an important small organic molecule, cyclopropane is widely used in drug design. In this paper, fifty-three amide derivatives containing cyclopropane were designed and synthesized by introducing amide groups and aryl groups into cyclopropane through the active splicing method, and their antibacterial and antifungal activities were evaluated in vitro. Among them, thirty-five compounds were new compounds, and eighteen compounds were known compounds (F14, F15, F18, F20-F26, F36, and F38-F44). Bioassay results disclosed that four, three, and nine of the compounds showed moderate activity against Staphylococcus aureus, Escherichia coli, and Candida albicans, respectively. Three compounds were sensitive to Candida albicans, with excellent antifungal activity (MIC80 = 16 µg/mL). The molecular docking results show that compounds F8, F24, and F42 have good affinity with the potential antifungal drug target CYP51 protein.

Chemical Modification of Pactamycin Leads to New Compounds with Retained Antimicrobial Activity and Reduced Toxicity.

Pactamycin (PCT), an antibiotic produced by Streptomyces pactum, is a five-membered ring aminocyclitol that is active against a variety of Gram-positive and Gram-negative microorganisms, as well as several animal tumor lines in culture and in vivo. Pactamycin targets the small ribosomal subunit and inhibits protein synthesis in bacteria, archaea, and eukaryotes, but due to its toxicity is used only as a tool for biochemical research. Prompted by the successful and well-established procedure for the derivatization of antibiotics, we modified pactamycin by tethering basic amino acids to the free primary amino group of the aminocyclitol ring. Specifically, lysine, ornithine, and histidine were conjugated via an amide bond, and the antimicrobial activity of the derivatives was evaluated both in vivo and in vitro. According to our results, their antimicrobial activity was maintained at almost equal levels, while their toxicity was reduced compared to the parent molecule. These findings suggest that the new pactamycin derivatives can be considered as promising pharmacophores for the development of new antimicrobials that are able to combat the dangerously increasing resistance of pathogens to antibiotics.

Naturally Occurring Xanthones and Their Biological Implications.

Xanthones are chemical substances in higher plants, marine organisms, and lower microorganisms. The most prevalent naturally occurring sources of xanthones are those belonging to the families Caryophyllaceae, Guttiferae, and Gentianaceae. Structurally, xanthones (9H xanthan-9-one) are heterocyclic compounds with oxygen and a γ-pyrone component. They are densely packed with a two-benzene ring structure. The carbons in xanthones are numbered from their nucleus and biosynthetic construct. They have mixed shikimate-acetate (higher plants) and acetate-malonate (lower organisms) biosynthetic origins, which influence their classification. Based on the level of oxidation of the C-ring, they are classified into monomers, dimers, and heterodimers. While based on the level of oxygenation or the type of ring residue, they can be categorized into mono-, di-, tri-, tetra-, penta- and hexa-oxygenated xanthones, bis-xanthones, prenylated and related xanthones, xanthonolignoids, and other miscellaneous xanthones. This structural diversity has made xanthones exhibit considerable biological properties as promising antioxidant, antifungal, antimicrobial, and anticancer agents. Structure-activity relationship studies suggest C-1, C-3, C-6, and C-8 as the key positions that influence the biological activity of xanthones. Furthermore, the presence of functional groups, such as prenyl, hydroxyl, glycosyl, furan, and pyran, at the key positions of xanthones, may contribute to their spectrum of biological activity. The unique chemical scaffolds of xanthones, their notable biological activities, and the structure-activity relationships of some lead molecules were discussed to identify lead molecules as possible drug candidates.