Search Results (13)

The growing threat of antimicrobial resistance has intensified the search for new bioactive compounds, particularly in extreme environments such as Antarctica. Streptomyces fildesensis So13.3, isolated from Antarctic soil, harbours a biosynthetic gene cluster (BGC) associated with actinomycin D production, an antibiotic with biomedical relevance. This study investigates the regulatory role of TetR/AcrR transcription factors encoded within this biosynthetic gene cluster (BGC), focusing on their structural features and expression under different nutritional conditions. Additionally, we propose that repressing an active pathway could lead to the activation of silent biosynthetic routes, and our in-silico analysis provides a foundation for selecting key mutations and experimentally validating this strategy. Expression analysis revealed that TetR-279, in particular, was upregulated in ISP4 and IMA media, suggesting its participation in nutrient-dependent BGC regulation. Structural modelling identified key differences between TetR-206 and TetR-279, with the latter containing a tetracycline-repressor-like domain. Molecular dynamics simulations confirmed TetR-279’s structural stability but showed that the S166P CRISPy-web-guided mutation considerably affected its flexibility, while V167A and V167I had modest effects. These results underscore the importance of integrating omics, structural prediction, and gene editing to evaluate and manipulate transcriptional regulation in non-model bacteria. Targeted disruption of TetR-279 may derepress actinomycin biosynthesis, enabling access to silent or cryptic secondary metabolites with potential pharmaceutical applications. Full article

Algae, despite being labeled as an underexplored biological source of chemical constituents, remain inadequately studied in terms of their metabolism. Metabolomics has emerged as a high-throughput technology to investigate the full metabolic profile of samples that could aid in the understanding and characterization of algae. By delving into their primary composition, particularly polysaccharides and phycobiliproteins, alongside secondary metabolites like polyphenols and pigments, researchers can uncover not only their rheological and nutritional properties but also their diverse biological activities. Given the growing interest in algae in food and related industries, innovative approaches should be explored to enhance the value of their functional components. In this sense, in the context of contemporary in-silico studies, metabolomics should be paired with computational methodologies, to develop novel techniques for studying biomolecular interactions. Molecular docking has emerged, with the function of predicting the atomic-level interaction between small molecules (ligands) and target proteins (proteins). This synergistic approach integrating both technologies could allow us to characterize algal profiles, evaluate their potential for bioactive properties, and better understand their metabolism. This work explores the development of metabolomic and computational strategies targeted toward the functional characterization of algae. By harnessing these technologies, we can unlock new possibilities for using algae in various industrial applications, paving the way for sustainable and innovative solutions in the future. Full article

Wound infections became a great challenge, especially after the emergence of bacterial resistance to commonly used antibiotics. Medicinal plants can be the source of alternative antibacterial agents effective against multi drug resistant (MDR) bacteria. This research aimed to evaluate the effectiveness of different Silybum marianum seed extracts in fighting MDR bacteria that infect wounds. First, thirty purified bacterial cultures obtained from superficial, infected wounds were subjected to antibiotic sensitivity tests. The selected MDR isolates were then used to test the antimicrobial effects of different S. marianum seed extracts. The most potent extract was evaluated for its impact on the ultrastructure of the cells of sensitive bacterial isolates using transmission electron microscopy (TEM). The bioactive ingredients of this extract were analyzed by means of gas chromatography–mass spectroscopy (GC–MS). Then, in-silico absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties were predicted for the main components. The results indicated that four out of 30 bacterial isolates were considered MDR bacteria. Primary morphological features of colonies, secondary (automatic) identification using the Biomerieux Vitek 2 System, and 16S rRNA sequencing of the four isolates confirmed that they represent Staphylococcus aureus, Stenotrophomonas maltophilia, Klebsiella pneumoniae, and Escherichia coli. Among different extracts of S. marianum seeds, ethanol extract showed the strongest inhibitory effect on both Gram-positive and Gram-negative bacteria, with minimum inhibitory concentration (MIC) values between 9.375 and 1.172 mg/mL. However, at concentrations four times higher, this extract was unable to kill bacterial cells, indicating that it had a bacteriostatic effect on the tested MDR strains. TEM revealed denaturation and distorted cell ultrastructure in S. aureus and S. maltophilia after exposure to ethanol extract. In addition, GC–MS analysis of the ethanol extract identified nine compounds known to have important biological activities, and ADMET analysis showed good drug-likeness for two of these compounds. Consequently, S. marianum seeds could be a good source of alternative bacteriostatic agents effective against MDR bacterial strains that cause wound infections. Full article

Prunus mahaleb L., also known as white mahaleb, and native to the Kurdistan region of Iraq, has significant nutraceutical and therapeutic ingredients. The seeds are rich in conjugated fatty acids with small quantities of cyanogenic glycosides, coumarin derivatives, and flavonoids. The contents of the seeds were extracted with the Soxhlet apparatus using n-hexane and petroleum ether solvents, separately. Gas chromatography-mass spectrometry (GC-MS) was used to recognize the chemical composition of the compounds. The radical scavenging activity was performed for the total extracts from n-hexane and petroleum ether solvents using 2,2-diphenyl-1 picrylhydrazyl (DPPH) assay and compared with quercetin as a positive control. Furthermore, molecular docking was performed for the identified compounds against five enzymes that have main roles in intracellular oxidation. Afterwards, drug-like properties and bioactivity predictions were applied for all compounds using Molinspiration software. The results showed four phthalate derivatives, six saturated fatty acids (SFAs), five monounsaturated fatty acids (MUFAs), and three polyunsaturated fatty acids (PUFAs). The n-hexane extract showed competitive antioxidant activity with quercetin and the in-silico studies suggested a notable antioxidant activity of the seed oil contents with apparent drug-likeness properties. Further studies are required to separate the extracts, then perform in vitro antioxidant activity on the compounds. Full article

Fenebrutinib is an orally available Bruton tyrosine kinase inhibitor. It is currently in multiple phase III clinical trials for the management of B-cell tumors and autoimmune disorders. Elementary in-silico studies were first performed to predict susceptible sites of metabolism and structural alerts for toxicities by StarDrop WhichP450™ module and DEREK software; respectively. Fenebrutinib metabolites and adducts were characterized in-vitro in rat liver microsomes (RLM) using MS3 method in Ion Trap LC-MS/MS. Formation of reactive and unstable intermediates was explored using potassium cyanide (KCN), glutathione (GSH) and methoxylamine as trapping nucleophiles to capture the transient and unstable iminium, 6-iminopyridin-3(6H)-one and aldehyde intermediates, respectively, to generate a stable adducts that can be investigated and analyzed using mass spectrometry. Ten phase I metabolites, four cyanide adducts, five GSH adducts and six methoxylamine adducts of fenebrutinib were identified. The proposed metabolic reactions involved in formation of these metabolites are hydroxylation, oxidation of primary alcohol to aldehyde, n-oxidation, and n-dealkylation. The mechanism of reactive intermediate formation of fenebrutinib can provide a justification of the cause of its adverse effects. Formation of iminium, iminoquinone and aldehyde intermediates of fenebrutinib was characterized. N-dealkylation followed by hydroxylation of the piperazine ring is proposed to cause the bioactivation to iminium intermediates captured by cyanide. Oxidation of the hydroxymethyl group on the pyridine moiety is proposed to cause the generation of reactive aldehyde intermediates captures by methoxylamine. N-dealkylation and hydroxylation of the pyridine ring is proposed to cause formation of iminoquinone reactive intermediates captured by glutathione. FBB and several phase I metabolites are bioactivated to fifteen reactive intermediates which might be the cause of adverse effects. In the future, drug discovery experiments utilizing this information could be performed, permitting the synthesis of new drugs with better safety profile. Overall, in silico software and in vitro metabolic incubation experiments were able to characterize the FBB metabolites and reactive intermediates using the multistep fragmentation capability of ion trap mass spectrometry. Full article

The common octopus is a cephalopod species subject to active fisheries, with great potential in the aquaculture and food industry, and which serves as a model species for biomedical and behavioral studies. The analysis of the skin mucus allows us to study their health in a non-invasive way, by using a hardly exploited discard of octopus in the fishing sector. A shotgun proteomics approach combined with liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) using an Orbitrap-Elite instrument was used to create a reference dataset from octopus skin mucus. The final proteome compilation was investigated by integrated in-silico studies, including Gene Ontology (GO), the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, network studies, and prediction and characterization analysis of potential bioactive peptides. This work presents the first proteomic analysis of the common octopus skin mucus proteome. This library was created by merging 5937 identified spectra of 2038 different peptides. A total of 510 non-redundant proteins were identified. Obtained results show proteins closely related to the defense, which highlight the role of skin mucus as the first barrier of defense and the interaction with the environment. Finally, the potential of the bioactive peptides with antimicrobial properties, and their possible application in biomedicine, pharmaceutical, and nutraceutical industry was addressed. Full article

Androgenetic Alopecia (AGA) occurs due to over-response to androgens causing severe hair loss on the scalp, and requires the development of new and efficient drugs to treat this condition. This study explores and identifies secondary metabolites from Sansevieriatrifasciata Prain using the LC-MS/MS and in-silico method. The inhibitory activity of bioactive compounds from S. trifasciata Prain against androgen receptors (PDB ID: 4K7A) was evaluated molecularly using docking and dynamics studies by comparing their binding energies, interactions, and stability with minoxidil. The results of the LC-MS/MS analysis identified Methyl pyrophaeophorbide A (1), Oliveramine (2), (2S)-3′, 4′-Methylenedioxy-5, 7-dimethoxyflavane (3), 1-Acetyl-β-carboline (4), Digiprolactone (5), Trichosanic acid (6) and Methyl gallate (7) from the leaves subfraction of this plant. Three alkaloid compounds (compounds 1, 3, and 4), and one flavonoid (compound 2), had lower docking scores of −7.0, −5.8, −5.2, and −6.3 kcal/mol, respectively. The prediction of binding energy using the MM-PBSA approach ensured that the potency of the four compounds was better than minoxidil, with energies of −66.13, −59.36, −40.39, and −40.25 kJ/mol for compounds 1, 3, 2, and 4, respectively. The dynamics simulation shows the stability of compound 1 based on the trajectory analysis for the 100 ns simulation. This research succeeded in identifying the compound and assessing the anti-alopecia activity of Sansevieria trifasciata Prain. Seven compounds were identified as new compounds never reported in Sansevieria trifasciata Prain. Four compounds were predicted to have better anti-alopecia activity than minoxidil in inhibiting androgen receptors through an in silico approach. Full article

Bioinformatics as a newly emerging discipline is considered nowadays a reference to characterize the physicochemical and pharmacological properties of the actual biocompounds contained in plants, which has helped the pharmaceutical industry a lot in the drug development process. In this study, a bioinformatics approach known as in silico was performed to predict, for the first time, the physicochemical properties, ADMET profile, pharmacological capacities, cytotoxicity, and nervous system macromolecular targets, as well as the gene expression profiles, of four compounds recently identified from Centaurea tougourensis via the gas chromatography–mass spectrometry (GC–MS) approach. Thus, four compounds were tested from the n-butanol (n-BuOH) extract of this plant, named, respectively, Acridin-9-amine, 1,2,3,4-tetrahydro-5,7-dimethyl- (compound 1), 3-[2,3-Dihydro-2,2-dimethylbenzofuran-7-yl]-5-methoxy-1,3,4-oxadiazol-2(3H)-one (compound 2), 9,9-Dimethoxybicyclo[3.3.1]nona-2,4-dione (compound 3), and 3-[3-Bromophenyl]-7-chloro-3,4-dihydro-10-hydroxy-1,9(2H,10H)-acridinedione (compound 4). The insilico investigation revealed that the four tested compounds could be a good candidate to regulate the expression of key genes and may also exert significant cytotoxic effects against several tumor celllines. In addition, these compounds could also be effective in the treatment of some diseases related to diabetes, skin pathologies, cardiovascular, and central nervous system disorders. The bioactive compounds of plant remain the best alternative in the context of the drug discovery and development process. Full article

Novel flavanones that incorporate chromene motifs are synthesized via a one-step multicomponent reaction. The structures of the new chromenes are elucidated by using IR, ¹H-NMR, ¹³C-NMR, ¹H-¹H COSY, HSQC, HMBC, and elemental analysis. The new compounds are screened for their in vitro antimicrobial and cytotoxic activities. The antimicrobial properties are investigated and established against seven human pathogens, employing the agar well diffusion method and the minimum inhibitory concentrations. A majority of the assessed derivatives are found to exhibit significant antimicrobial activities against most bacterial strains, in comparison to standard reference drugs. Moreover, their cytotoxicity is appraised against four different human carcinoma cell lines: human colon carcinoma (HCT-116), human hepatocellular carcinoma (HepG-2), human breast adenocarcinoma (MCF-7), and adenocarcinoma human alveolar basal epithelial cell (A-549). All the desired compounds are subjected to in-silico studies, forecasting their drug likeness, bioactivity, and the absorption, distribution, metabolism, and excretion (ADME) properties prior to their synthetic assembly. The in-silico molecular docking evaluation of all the targeted derivatives is undertaken on gyrase B and the cyclin-dependent kinase. The in-silico predicted outcomes were endorsed by the in vitro studies. Full article

Jumbo squid (Dosidicus gigas) is one of the largest cephalopods, and represents an important economic fishery in several regions of the Pacific Ocean, from southern California in the United States to southern Chile. Large and considerable discards of this species, such as skin, have been reported to constitute an important source of potential by-products. In this paper, a shotgun proteomics approach was applied for the first time to the characterization of the jumbo squid (Dosidicus gigas) skin proteome. A total of 1004 different peptides belonging to 219 different proteins were identified. The final proteome compilation was investigated by integrated in-silico studies, including gene ontology (GO) term enrichment, pathways, and networks studies. Potential new valuable bioactive peptides such as antimicrobial, bioactive collagen peptides, antihypertensive and antitumoral peptides were predicted to be present in the jumbo squid skin proteome. The integration of the global proteomics results and the bioinformatics analysis of the jumbo squid skin proteome show a comprehensive knowledge of this fishery discard and provide potential bioactive peptides of this marine by-product. Full article

In in-silico prediction for molecular binding of human genomes, promising results have been demonstrated by deep neural multi-task learning due to its strength in training tasks with imbalanced data and its ability to avoid over-fitting. Although the interrelation between tasks is known to be important for successful multi-task learning, its adverse effect has been underestimated. In this study, we used molecular interaction data of human targets from ChEMBL to train and test various multi-task and single-task networks and examined the effectiveness of multi-task learning for different compositions of targets. Targets were clustered based on sequence similarity in their binding domains and various target sets from clusters were chosen. By comparing the performance of deep neural architectures for each target set, we found that similarity within a target set is highly important for reliable multi-task learning. For a diverse target set or overall human targets, the performance of multi-task learning was lower than single-task learning, but outperformed single-task for the target set containing similar targets. From this insight, we developed Multiple Partial Multi-Task learning, which is suitable for binding prediction for human drug targets. Full article

Background: Clinacanthus nutans (C. nutans) is an Acanthaceae herbal shrub traditionally consumed to treat various diseases including diabetes in Malaysia. This study was designed to evaluate the α-glucosidase inhibitory activity of C. nutans leaves extracts, and to identify the metabolites responsible for the bioactivity. Methods: Crude extract obtained from the dried leaves using 80% methanolic solution was further partitioned using different polarity solvents. The resultant extracts were investigated for their α-glucosidase inhibitory potential followed by metabolites profiling using the gas chromatography tandem with mass spectrometry (GC-MS). Results: Multivariate data analysis was developed by correlating the bioactivity, and GC-MS data generated a suitable partial least square (PLS) model resulting in 11 bioactive compounds, namely, palmitic acid, phytol, hexadecanoic acid (methyl ester), 1-monopalmitin, stigmast-5-ene, pentadecanoic acid, heptadecanoic acid, 1-linolenoylglycerol, glycerol monostearate, alpha-tocospiro B, and stigmasterol. In-silico study via molecular docking was carried out using the crystal structure Saccharomyces cerevisiae isomaltase (PDB code: 3A4A). Interactions between the inhibitors and the protein were predicted involving residues, namely LYS156, THR310, PRO312, LEU313, GLU411, and ASN415 with hydrogen bond, while PHE314 and ARG315 with hydrophobic bonding. Conclusion: The study provides informative data on the potential α-glucosidase inhibitors identified in C. nutans leaves, indicating the plant’s therapeutic effect to manage hyperglycemia. Full article

A facile bottom-up “green” synthetic route of gold nanoparticles (Au NPs) is described, using a leaf extract of the Malvaceae plant Corchorus olitorius as a reducing and stabilizing agent. The size and shape of the obtained nanoparticles were modulated by varying the amounts of the metal salt and the broth extract in the reaction medium. Only one hour was required for the complete conversion to Au NPs, suggesting that the reaction rate was higher or comparable to those of nanoparticles synthesized by chemical methods. The obtained nanoparticles were characterized by UV–visible spectroscopy, transmission electron microscopy (TEM), X-ray diffraction (XRD), Fourier-transform infrared (FTIR) spectroscopy, and thermal gravimetric analysis (TGA). While infrared spectroscopy was employed to characterize the various functional groups in the organic layer that stabilized the particles, TEM images were used to optimize the conditions for NPs growth. A low concentration of the C. olitorius extract yielded mixed triangular and hexagonal shapes; in contrast, quasi-spherical shapes of Au NPs with an average size of 37–50 nm were obtained at a higher extract broth concentration. The Au NPs displayed Surface Plasmon Resonance (SPR) bands at 535 nm. An in vitro cytotoxic assay of the biocompatible Au NPs revealed a strong cytotoxic activity in three human cancer cell lines, namely, colon carcinoma HCT-116, hepatocellular carcinoma HepG-2, and breast adenocarcinoma MCF-7. In-silico bioactivity, drug-likeness, and ADMET (Absorption, Distribution, Metabolism, Excretion, and Toxicity) predictions were conducted in order to examine the pharmacokinetic behavior of the compounds present in the C. olitorius extract. Full article