Search Results (9)

Glioblastoma is the most common and aggressive brain tumor in adults. However, due to the limitations of conventional treatments, as well as their side effects, there is a need to develop more effective and less harmful therapy strategies. There is evidence that plants endemic to northern Mexico possess biological activities that positively impact human health, particularly against cancer. Echinocereus engelmannii and Echinocereus pectinatus are cacti from the north of Mexico that produce bioactive compounds with antitumor activity. We obtained methanol extracts from previously isolated and fermented microorganisms associated with these cacti. Cell lines of extracts with cytotoxicity against glioblastoma cells U87, neuroblastoma cells SH-S5Y5, and Schwann neuronal cells (healthy control) were evaluated, using a colorimetric 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazole bromide (MTT) reduction technique. The selective cytotoxicity extracts were analyzed using liquid chromatography tandem mass spectrometry (LC/MS²). We isolated 19 endophytic and soil-associated microorganisms from both cacti. Two of them were selected for their high percentages of tumor growth inhibition. The microorganism ES4 possessed the best activity with an IC₅₀ of 17.31 ± 1.70 µg/mL and a selectivity index of 3.11. We identified the bacterium Stenotrophomonas maltophilia by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) from the most active microorganisms against tumor growth. LC/MS² characterized the HS4 extract, and the most abundant group (50.0%) identified included carboxylic acids and derivatives, particularly bisgerayafolin A, Cyclo (Pro-Leu), maculosin, and tryptophan. In conclusion S. maltophilia extract inhibit the growth of glioma cells, showing greater sensitivity in the U87 cell line. Full article

The investigation of melanogenesis and tyrosinase inhibitors is essential for developing safe and effective natural compounds to treat pigmentation disorders. This study aimed to evaluate the effects of maculosin, a cyclic dipeptide composed of tyrosine and proline, on melanin production and tyrosinase activity using the B16F10 melanoma cell model, while elucidating its mechanism of action through molecular docking and molecular dynamics (MD) simulations. Experimental results demonstrated that maculosin inhibited intracellular melanin content and tyrosinase activity in a concentration-dependent manner in B16F10 melanoma cells. Molecular docking analyses revealed that maculosin exhibited high binding affinities with mushroom tyrosinase (mTYR), tyrosinase-related protein 1 (TYRP1), and Bacillus megaterium tyrosinase (BmTYR) with binding energies of −7.7, −6.8, and −7.5 kcal/mol, respectively. Furthermore, MD simulations confirmed the structural stability and dynamic flexibility of maculosin–protein complexes, as indicated by RMSD, RMSF, Rg, SASA, hydrogen bond interactions, PCA, and DCCM analyses. Binding free energy calculations using the MM/PBSA method showed that maculosin exhibited binding energies of −28.76 kcal/mol with mTYR and −22.23 kcal/mol with TYRP1, outperforming standard co-crystal inhibitors such as tropolone (−12.47 kcal/mol) and kojic acid (−12.73 kcal/mol). Critical residues, including VAL-283 and HIS-263 in mTYR and HIS-381, GLY-389, and THR-391 in TYRP1, were identified as key contributors to maculosin binding, corroborating molecular docking findings and displaying strong correlations in DCCM analyses. Collectively, these results suggest that maculosin is a highly promising candidate for the treatment of pigmentation disorders, offering significant inhibitory effects on melanogenesis and tyrosinase activity. Full article

Branched broomrape (Phelipanche ramosa (L.) Pomel), an obligate parasitic weed with a wide host range, is known for its devasting effects on many crops worldwide. Soil fungi, notably Fusarium sp., are described as pathogenic to broomrape, while the hypothesis of the phytotoxicity of fusaric acid produced by F. verticillioides for parasitic weeds of the genus Orobanche has been proposed. Using image analysis and untargeted metabolomics, this study investigated fungal metabolites phytotoxic for P. ramosa and produced by the F. venenatum MIAE02836 strain, isolated from symptomatic broomrapes and identified as a promising candidate for broomrape biocontrol. Phytotoxicity tests of crude extracts from the fungus alone or in interaction with broomrape on P. ramosa microcalli and quantification of necrosis by image analysis confirmed the phytotoxic potential of F. venenatum MIAE02836 metabolites towards the early developmental stages of P. ramosa. Data analysis of a non-targeted metabolomics approach revealed numerous metabolites produced by F. venenatum MIAE02836. Four of them, accumulated during interaction with the parasitic plant, are known for their phytotoxic potential: maculosin, cyclo(Leu-Phe), phenylalanyl-D-histidine and anguidine. These results suggest that combining image acquisition of the microcalli screening test and untargeted metabolomic approach is an interesting and relevant method to characterize phytotoxic fungal metabolites. Full article

A potential strain, Paenibacillus sp. JNUCC32, was isolated and subjected to whole-genome sequencing. Genome functional annotation revealed its active metabolic capabilities. This study aimed to investigate the pivotal secondary metabolites in the biological system. Fermentation and extraction were performed, resulting in the isolation of seven known compounds: tryptophol (1), 3-(4-hydroxyphenyl)propionic acid (2), ferulic acid (3), maculosin (4), brevianamide F (5), indole-3-acetic acid (6), and butyric acid (7). Tryptophol exhibited favorable pharmacokinetic properties and demonstrated certain tyrosinase inhibitory activity (IC₅₀ = 999 μM). For further analysis of its inhibition mechanism through molecular docking and molecular dynamics (MD) simulation, tryptophol formed three hydrogen bonds and a pro-Michaelis complex with tyrosinase (binding energy = −5.3 kcal/mol). The MD simulation indicated favorable stability for the tryptophol–mushroom tyrosinase complex, primarily governed by hydrogen bond interactions. The crucial residues VAL-283 and HIS-263 in the docking were also validated. This study suggests tryptophol as a potential candidate for antibrowning agents and dermatological research. Full article

Antibiotic growth promoters (AGPs) suppress the growth of infectious pathogens. These pathogens negatively impact agricultural production worldwide and often cause health problems if left untreated. Here, we evaluate six Bacillus strains (BPR-11, BPR-12, BPR-13, BPR-14, BPR-16 and BPR-17), which are known for their ability to survive harsh environmental conditions, as AGP replacements in animal feed. Four of these Bacillus strains (BPR-11, BPR-14, BPR-16 and BPR-17) showed antimicrobial activity against the pathogenic strains Clostridium perfringens, Escherichia coli and Staphylococcus aureus at 25 μg/mL, with BPR-16 and BPR-17 also able to inhibit Pseudomonas aeruginosa and Salmonella enterica at 100 μg/mL. Further chemical investigation of BPR-17 led to the identification of eight metabolites, namely C16, C15, C14 and C13 surfactin C (1–4), maculosin (5), maculosine 2 (6), genistein (7) and daidzein (8). Purified compounds (1–4) were able to inhibit all the tested pathogens with MIC values ranging from 6.25 to 50 μg/mL. Maculosin (5) and maculosine 2 (6) inhibited C. perfringens, E. coli and S. aureus with an MIC of 25 μg/mL while genistein (7) and daidzein (8) showed no activity. An animal trial involving feeding BPR-11, BPR-16 and BPR-17 to a laboratory poultry model led to an increase in animal growth, and a decrease in feed conversion ratio and mortality. The presence of surfactin C analogues (3–4) in the gut following feeding with probiotics was confirmed using an LC–MS analysis. The investigation of these Bacillus probiotics, their metabolites, their impacts on animal performance indicators and their presence in the gastrointestinal system illustrates that these probiotics are effective alternatives to AGPs. Full article

Finding new antibacterial agents from natural products is urgently necessary to address the growing cases of antibiotic-resistant pathogens. Actinomycetes are regarded as an excellent source of therapeutically important secondary metabolites including antibiotics. However, they have not yet been characterized and explored in great detail for their utility in developing countries such as Nepal. In silico molecular docking in addition to antimicrobial assays have been used to examine the efficacy of chemical scaffolds biosynthesized by actinomycetes. This paper depicts the characterization of actinomycetes based on their morphology, biochemical tests, and partial molecular sequencing. Furthermore, antimicrobial assays and mass spectrometry-based metabolic profiling of isolates were studied. Seventeen actinomycete-like colonies were isolated from ten soil samples, of which three isolates showed significant antimicrobial activities. Those isolates were subsequently identified to be Streptomyces species by partial 16S rRNA gene sequencing. The most potent Streptomyces species_SB10 has exhibited an MIC and MBC of 1.22 μg/mL and 2.44 μg/mL, respectively, against each Staphylococcus aureus and Shigella sonnei. The extract of S. species_SB10 showed the presence of important metabolites such as albumycin. Ten annotated bioactive metabolites (essramycin, maculosin, brevianamide F, cyclo (L-Phe-L-Ala), cyclo (L-Val-L-Phe), cyclo (L-Leu-L-Pro), cyclo (D-Ala-L-Pro), N6, N6-dimethyladenosine, albumycin, and cyclo (L-Tyr-L-Leu)) were molecularly docked against seven antimicrobial target proteins. Studies on binding energy, docking viability, and protein-ligand molecular interactions showed that those metabolites are responsible for conferring antimicrobial properties. These findings indicate that continuous research on the isolation of the Streptomyces species from Nepal could lead to the discovery of novel and therapeutically relevant antimicrobial agents in the future. Full article

Agar accounts for ~60% of the dry weight of some red macroalgae, and the breakdown of this kind of polysaccharide releases high-value compounds; therefore, the resource utilization of agar is of great significance to improve the added value of these macroalgae. Herein, Alteromonas macleodii QZ9-9 isolated from tropical Gracilaria hainanensis in Hainan Island was characterized as an agarolytic bacterium, which displayed a high agar-degrading activity. The highest diameters of the degradation zones of the A. macleodii QZ9-9 and its extracellular-agarase (12.16 U/mL) were 41.46 mm and 22.89 mm, respectively, and the first-order degradation rate constants of those were 0.02 h⁻¹ and 0.77 U⁻¹, respectively. Importantly, the fermentation products of A. macleodii QZ9-9 exhibited antioxidant activity, and the peak of DPPH scavenging activity of 50 h fermentation products of this strain was up to 50.79% in the reaction for 1 h; the DPPH scavenging activity of low molecule metabolites (≤3 kDa) in particular was up to ~85.85%. A total of 766 metabolites were detected in the low molecule metabolites by metabolomics. The peptide-like metabolites, such as prolyl–histidine, isoleucyl–histidine, isoleucyl–proline and arginyl–proline, and the antioxidant maculosin were found in the top 20 metabolites with relatively high abundance. Additionally, the antioxidant activity of maculosin was further verified in this work. We concluded that the low molecule metabolites of A. macleodii QZ9-9 with relatively high antioxidant activity are interesting candidates for preparing desirable non-toxic antioxidants, thereby facilitating the high value-added utilization of macroalgae in the fields of cosmetic, food preservation, and pharmaceutical industries. Full article

Alternaria is a ubiquitous fungal genus in many ecosystems, consisting of species and strains that can be saprophytic, endophytic, or pathogenic to plants or animals, including humans. Alternaria species can produce a variety of secondary metabolites (SMs), especially low molecular weight toxins. Based on the characteristics of host plant susceptibility or resistance to the toxin, Alternaria phytotoxins are classified into host-selective toxins (HSTs) and non-host-selective toxins (NHSTs). These Alternaria toxins exhibit a variety of biological activities such as phytotoxic, cytotoxic, and antimicrobial properties. Generally, HSTs are toxic to host plants and can cause severe economic losses. Some NHSTs such as alternariol, altenariol methyl-ether, and altertoxins also show high cytotoxic and mutagenic activities in the exposed human or other vertebrate species. Thus, Alternaria toxins are meaningful for drug and pesticide development. For example, AAL-toxin, maculosin, tentoxin, and tenuazonic acid have potential to be developed as bioherbicides due to their excellent herbicidal activity. Like altersolanol A, bostrycin, and brefeldin A, they exhibit anticancer activity, and ATX V shows high activity to inhibit the HIV-1 virus. This review focuses on the classification, chemical structure, occurrence, bioactivity, and biosynthesis of the major Alternaria phytotoxins, including 30 HSTs and 50 NHSTs discovered to date. Full article

Microbes are natural chemical factories and their metabolome comprise diverse arrays of chemicals. The genus Xanthomonas comprises some of the most important plant pathogens causing devastating yield losses globally and previous studies suggested that species in the genus are untapped chemical minefields. In this study, we applied an untargeted metabolomics approach to study the metabolome of a globally spread important xanthomonad, X. perforans. The pathogen is difficult to manage, but recent studies suggest that the small molecule carvacrol was efficient in disease control. Bacterial strains were treated with carvacrol, and samples were taken at time intervals (1 and 6 h). An untreated control was also included. There were five replicates for each sample and samples were prepared for metabolomics profiling using the standard procedure. Metabolomics profiling was carried out using a thermo Q-Exactive orbitrap mass spectrometer with Dionex ultra high-performance liquid chromatography (UHPLC) and an autosampler. Annotation of significant metabolites using the Metabolomics Standards Initiative level 2 identified an array of novel metabolites that were previously not reported in Xanthomonas perforans. These metabolites include methoxybrassinin and cyclobrassinone, which are known metabolites of brassicas; sarmentosin, a metabolite of the Passiflora-heliconiine butterfly system; and monatin, a naturally occurring sweetener found in Sclerochiton ilicifolius. To our knowledge, this is the first report of these metabolites in a microbial system. Other significant metabolites previously identified in non-Xanthomonas systems but reported in this study include maculosin; piperidine; β-carboline alkaloids, such as harman and derivatives; and several important medically relevant metabolites, such as valsartan, metharbital, pirbuterol, and ozagrel. This finding is consistent with convergent evolution found in reported biological systems. Analyses of the effect of carvacrol in time-series and associated pathways suggest that carvacrol has a global effect on the metabolome of X. perforans, showing marked changes in metabolites that are critical in energy biosynthesis and degradation pathways, amino acid pathways, nucleic acid pathways, as well as the newly identified metabolites whose pathways are unknown. This study provides the first insight into the X. perforans metabolome and additionally lays a metabolomics-guided foundation for characterization of novel metabolites and pathways in xanthomonad systems. Full article