Search Results (531)

This study aimed to evaluate the physicochemical characterization and antibacterial activity of the essential oil (EO) extracted from the leaves of Mentha rotundifolia (L.) Huds. Molecular interactions between bioactive ligand compounds, target bacterial proteins and DNA gyrase subunit B (GyrB), as well as an in silico ADMET prediction study, were also conducted. The EO was obtained by hydrodistillation of the plant leaves. The Gas Chromatography–Tandem Mass Spectrometry (GC-MS/MS) analysis revealed Rotundifolone (27.95%) and carvacrol (19.48%) as the major constituents. Other components identified included Piperitenone (6.09%), Cinerolon (4.73%), and Pulegone (4.47%). Antibacterial activity was assessed against six bacterial strains: Enterococcus faecalis CIP 103214, Salmonella Typhi CIP 5535, Staphylococcus aureus ATCC 9144, Bacillus cereus ATCC 33019, Streptococcus agalactiae IPM 24842, and Providencia alcalifaciens CIP 82.90T. The disk diffusion assay showed a strong inhibitory effect against E. faecalis (inhibition zone: 19.66 ± 0.3 mm), while the lowest minimum inhibitory concentration (MIC) was observed for B. cereus (0.58 ± 0.01 µL/mL). The time-kill kinetics assay showed a progressive inactivation of all tested bacterial strains after their exposure to EO for 8 h at MICs. Furthermore, Molecular docking showed remarkable affinities between EO components, target proteins and DNA gyrase subunit B (GyrB). Moreover, the in silico ADMET predictions provided preliminary insights into the safety-related properties of the major EO components. In addition, EO compounds have the potential to interact with bacterial structures. These findings highlight the in vitro antibacterial potential of the M. rotundifolia EO and suggest its promise as a natural source of bioactive compounds. Full article

Background: Guanine-rich DNA regions can fold into G-quadruplex (G4) structures, which are prevalent in telomeres and oncogene promoters, making them attractive targets for anticancer therapeutics. Small molecules capable of selectively stabilizing G4 DNA can disrupt telomerase activity and oncogene expression, offering a promising strategy for cancer intervention. Methods: A rationally designed series of DPPZ–anhydride-conjugated ligands (1 and 2) and their corresponding quaternized derivatives (1-q and 2-q) were synthesized to investigate the combined effects of π-extension, bromine substitution, and cationic modification on DNA recognition. The synthetic strategy relied on the incorporation of a highly planar DPPZ–anhydride scaffold to enhance π-surface area, followed by selective quaternization to introduce permanent positive charge and reinforce electrostatic interactions with the DNA backbone. All compounds were fully characterized by NMR and spectroscopic methods. The DNA-binding properties of the ligands were systematically evaluated toward duplex (ds-DNA) and G-quadruplex (G4-DNA) structures using UV–Vis absorption titration, fluorescence intercalator displacement (FID) assays, and competitive dialysis experiments. Quaternization markedly enhanced intrinsic binding constants and significantly reduced DC₅₀ values, particularly for G4-DNA. While bromine substitution increased overall binding affinity, it did not substantially improve topology selectivity. Among the series, compound 1-q exhibited the most favorable balance between affinity and G4 selectivity. Results: The interaction of the compounds with BSA was quantified using Stern–Volmer quenching constants, which demonstrated a clear trend of enhanced quenching efficiency upon modification. The binding strength followed a descending order of 1-q > 2-q > 1 > 2, highlighting the superior performance of the first series over the second. These findings indicate that the structural features of 1-q facilitate a more robust interaction within the hydrophobic pockets of the protein. Conclusions: Overall, the results demonstrate that strategic π-conjugation combined with electrostatic reinforcement provides an effective approach for the development of topology-selective DNA-binding ligands. Full article

Background: Breast cancer (BC) remains the most prevalent malignancy among women worldwide, with one in eight at risk during their lifetime. Platinum-based chemotherapeutic drugs, despite of their binding to the DNA of cancer cells, are plagued by toxicity and resistance, necessitating the need for safer and more effective alternatives, such as organometallic complexes. Both synthetic organometallic complexes and natural compounds have attracted attention in this regard. Organotin(IV) complexes are promising chemotherapeutics due to their structural versatility and bioactivity, while vitamins such as Vitamin D (VD) and Vitamin E (VE) exhibit antiproliferative, anti-inflammatory, and antioxidant properties, making them valuable candidates for combination therapy. Methodology: In this study, six novel organotin(IV) dithiocarbamate complexes [LMe₃Sn (Complex 1), LBu₃Sn (Complex 2), LPh₃Sn (Complex 3), LMe₂SnCl (Complex 4), LBu₂SnCl (Complex 5), and L₂Me₂Sn (Complex 6), where L = (E)-4-styrylpiperazine-1-carbodithioate], were synthesized and characterized by FT-IR, ¹H-, ¹³C-NMR, and elemental analysis. Results: Structural studies confirmed penta- and hexacoordination geometries. In silico docking against six BC-related proteins identified Complexes 2 and 4 with both vitamins as promising candidates, exhibiting strong binding affinities, with stable interaction profiles. However, integration of pharmacokinetic, antioxidant, and anti-inflammatory analyses highlighted Complex 4 with both vitamins as the most potent candidate owing to its superior ADME characteristics and balanced biological properties. Subsequent in vitro assays confirmed these findings, as Complex 4 demonstrated strong cytotoxic activity against both MCF-7 (>1.16-fold) and MDA-MB-231 (>1.46-fold) cell lines, surpassing the efficacy of cisplatin. Remarkably, co-administration of VD or VE with Complex 4 further enhanced its anticancer potential, with Chou–Talalay combination index values < 1 (0.66–0.91) indicating a synergistic interaction. Conclusions: Collectively, these results identify Complex 4 as a promising lead compound, and its synergistic activity with natural vitamins may promote cell death, likely through apoptosis induction and modulation of oxidative stress, underscoring its potential as an effective and less toxic therapeutic strategy for breast cancer management. Full article

Monkeypox virus (MPXV) is emerging as a global public health concern due to its nature of spread. There are limited treatment options, as the sole drug for treatment is lacking, highlighting the need for new therapeutic options. The use of computer-aided drugs discovery such as molecular docking, molecular dynamic (MD) simulations and post-simulation analysis are important tools in identifying potential compounds that can target specific proteins of the virus, such as DNA polymerase to stop virus replication. This study employed molecular docking and molecular simulation with the aim to identify potential inhibitors for MPXV treatment from the ZINC Database. Molecular docking was performed using PyRx 0.8 version after virtual screening of the ZINC database using the Tranches tool; then, toxicity prediction of the selected compounds was performed using the ProTox-3.0 web server. Molecular dynamics simulation was conducted using GROMACS version 4.5 to evaluate the structural stability and dynamic behavior of the protein–ligand complex for the best interacting compound. Furthermore, post-simulation analysis was conducted using standard GROMACS utilities for visualizing time-dependent properties from MD simulations. A total of 16 compounds were shortlisted based on their molecular docking scores and interaction profiles with the monkeypox virus DNA polymerase (PDB ID: 8HG1). The leading compound, ZINC000019418450, demonstrated strong binding affinity (−7.4 kcal/mol). According to post-simulation analysis, all top compounds formed between one and five hydrogen bonds and up to eleven hydrophobic contacts with residues within the active site, thus providing strong geometric and energetic evidence for binding stability. Notably, our identification of ZINC000104288636 as a Class 6 compound with an LD₅₀ of 23,000 mg/kg adds translational value by highlighting candidates with low predicted acute toxicity. Overall, this study lays a solid foundation for the rational design of next-generation monkeypox antiviral therapeutics. Future work is needed for experimental validation of prioritized compounds to assess their biochemical efficacy and pharmacological potential. Full article

The MADS-box transcription factor (TF) family constitutes a critical class of transcriptional regulators in plants, playing pivotal roles in diverse developmental processes. MIKC-type proteins represent Type II MADS-box TFs that widely function in regulating floral organ development and reproductive growth in plants. In this study, a total of 38 MIKC-type MADS TFs were identified from the sorghum genome, distributed across nine chromosomes. Based on sequence alignments and phylogenetic analysis, these 38 SbMIKC genes (SbMIKCs) were further classified into 10 distinct subfamilies. The expression profiling of these SbMIKCs across multiple tissues revealed five major patterns, among which SbMIKC17 exhibited relatively abundant transcript levels during grain development in sorghum. Further assays confirmed that the protein encoded by SbMIKC17 localizes to the nucleus without self-transactivation activity in yeast. Integrated results from DNA affinity purification sequencing (DAP-seq), dual-luciferase assays, and yeast one-hybrid experiments demonstrate that SbMIKC17 binds to the promoter of SbAGPS1 and activates its activity, as well as enhance the promoter activities of SbBt1, SbGBSSI, SbSSIIa, and SbISA1 simultaneously. Collectively, these findings suggest that the MIKC-type MADS member of SbMIKC17 serves as a potential transcriptional regulator in starch biosynthesis in sorghum. Full article

Monkeypox virus, a zoonotic DNA virus belonging to the Orthopoxvirus genus, has emerged as a global health issue because of its fast spread to 104 nations over six continents. In the current study, an immunoinformatics pipeline was used to design a multiepitope-based prophylactic vaccine targeting the A35R glycoprotein and E8L membrane proteins of the monkeypox virus. Selected target proteins were surface-exposed, non-homologous to the human proteome, and essential for viral pathogenesis. B-cell and T-cell (MHC-I and MHC-II) epitopes with high antigenicity (>0.5), non-allergenicity, non-toxicity, and highly soluble in water with strong affinity towards innate and adaptive receptors, were prioritized. Shortlisted epitopes were combined to design the final vaccine utilizing an adjuvant (50S ribosomal L7/L12) and appropriate linkers for improved immunogenicity. Population coverage analysis showed wide HLA representation with 83.57% (MHC-I) and 88.8% (MHC-II) global coverage, including 89.6% for West Africa and 87.3% for Central Africa. Docking analysis of the vaccine construct with the TLR-4 receptor revealed stable interactions (−695.6 kcal/mol). Molecular dynamics simulations and binding free energies further confirmed structural stability. Immune simulations predicted strong activation of both humoral and cellular immune responses. These results indicate that the designed multiepitope vaccine construct is a viable option for additional experimental validation against the monkeypox virus. Full article

Crop fungal and viral diseases cause annual economic losses exceeding USD 150 billion globally, demanding rapid, sensitive, and field-deployable diagnostic technologies. This review critically evaluates recent advances in electrochemical biosensing platforms for early crop pathogen detection, focusing on immunosensors, genosensors, aptasensors, and VOC-based systems. Reported analytical performances demonstrate ultralow detection capabilities, including 0.3 fg mL⁻¹ for viral coat proteins, 15 DNA copies for bacterial pathogens, 0.5 fg µL⁻¹ RNA detection for viroids, and nanomolar-level VOC sensing (35–62 nM), with response times ranging from 2 to 60 min. Comparative analysis reveals that genosensors and aptasensors generally achieve the lowest LODs due to nucleic acid amplification or high-affinity recognition, while immunosensors provide robust protein-level specificity validated against ELISA. Volatile organic compound (VOC) sensors enable non-invasive, pre-symptomatic monitoring but face specificity challenges. Despite strong laboratory performance, practical adoption is limited by matrix-derived electrochemical interference, environmental instability of biorecognition elements, workflow complexity, and insufficient standardization across studies. Emerging innovations, including magnetic bead enrichment, nanoporous and graphene-based electrodes, microfluidic integration, AI-assisted impedance interpretation, and biodegradable substrates, are progressively addressing these bottlenecks. This review emphasizes that successful field translation requires holistic workflow engineering, matrix-matched validation, and harmonized performance metrics rather than incremental sensitivity improvements alone. By integrating analytical chemistry, nanomaterials engineering, and agricultural decision-support frameworks, electrochemical biosensing platforms hold significant potential to enable decentralized, rapid, and sustainable crop disease management. Full article

Three new Mn(II) complexes with imidazo[1,2-a]pyridine derivatives were synthesized and structurally characterized in a solid state by single crystal X-ray diffraction, FT-IR and Raman spectroscopy, and thermal analyses. The investigated compounds include [Mn(3-Climpy)₂Cl₂(MeOH)₂] (1), [Mn(3-Brimpy)₂Cl₂(MeOH)₂] (2), and a rare double chloro-bridged coordination polymer [Mn(impy)₂Cl₂]_n (3). Spectroscopic studies were used to assess their potential stability in DMEM (Dulbecco’s Modified Eagle Medium), and encapsulation in Pluronic P-123 micelles improved their solubility in aqueous solution, as well as cellular uptake and selectivity. Biological evaluation revealed negligible cytotoxicity against most cancer and control cell lines, but unexpectedly high activity against pancreatic adenocarcinoma (PANC-1), exceeding that of cisplatin. Complex 2, bearing a bromine substituent in the imidazole ring, showed the strongest effects, correlating with enhanced intracellular accumulation, reactive oxygen species (ROS) generation, and mitochondrial membrane potential disruption. Molecular docking and protein binding assays demonstrated moderate affinity toward human serum albumin (HSA) and transferrin, whereas DNA interaction was weak and non-damaging. These results highlight the structure–activity relationship of Mn(II) imidazo[1,2-a]pyridine complexes and support their potential as targeted redox-active agents against pancreatic cancer, with polymeric encapsulation providing an effective strategy to enhance biological performance. Full article

Cisplatin’s chemotherapy is hindered by drug resistance and toxicity, making copper complexes a potential alternative. A novel copper(II) complex, [CuLBr], was synthesized from a tetradentate vicinal dioxime ligand (H₂L) and characterized. [CuLBr] features a distorted square pyramidal geometry with a CuN₄Br chromophore. DFT calculations showed a narrowed HOMO-LUMO gap and increased electrophilicity, enhancing its chemical reactivity. [CuLBr] exhibited potent biomimetic catalytic activity, functioning as an efficient superoxide dismutase mimic and catalase mimic. Biophysical studies (UV-Vis, fluorescence, and viscosity) demonstrated a strong, spontaneous affinity of [CuLBr] for calf thymus DNA and Human Serum Albumin, suggesting groove-binding and static quenching mechanisms. In vitro assays revealed superior anticancer activity against HepG-2, HCT-116, and MDA-MB-231 cell lines, with greater selectivity than the free ligand and doxorubicin. Molecular docking studies reveal a high binding affinity of [CuLBr] with key proteins, including ferredoxin-1 and VEGF. This may suggest potential dual mechanisms of action, involving the induction of cuproptosis and the inhibition of tumor angiogenesis. These findings position [CuLBr] as an effective multi-metal-based anticancer agent with advantageous selectivity. Full article

Corydalis impatiens (Papaveraceae) is a traditional Tibetan medicinal plant (“Pa Xia Ga”) whose mitochondrial genome evolution remains unexplored, particularly in the context of high-altitude adaptation. This study presents the first complete mitochondrial genome sequence of an alpine Corydalis species to establish a comparative framework with the lowland congener C. pauciovulata for investigating environment-associated mitochondrial evolution. Using Illumina sequencing and reference-guided assembly, we characterized a 688,959 bp circular genome containing 74 genes, with GC content variations reflecting functional compartmentalization—elevated in structural RNA genes (tRNAs: 51.24%; rRNAs: 52.79%) versus protein-coding genes (44.19%). We identified 719 RNA editing sites concentrated in NADH dehydrogenase genes, suggesting post-transcriptional optimization of respiratory complex I under hypoxic conditions. The genome harbors 50 dispersed repeats (7.50%) and 67 SSRs with A-rich predominance, providing species-specific markers for authenticating “Pa Xia Ga” in Tibetan medicine quality control. Phylogenomic analysis confirms close affinity with C. pauciovulata while resolving intrageneral relationships within Ranunculales. These findings establish a dual-reference system for distinguishing conserved genus-level features from altitude-associated adaptations, enabling future comparative mitogenomics across the 465-species genus and supporting DNA-based medicinal plant identification. Full article

Background/Objectives: Leishmaniasis is a disease affecting millions of people caused by parasites of the genus Leishmania. The GP63 protein of Leishmania infantum (LiGP63) is one of its major surface antigens and a main virulence factor, playing a role in the adhesion of extracellular promastigote stages to macrophages and in the survival of intracellular amastigotes. Methods: Here, DNA aptamers have been developed against LiGP63 through the systematic evolution of ligands by exponential enrichment. Results: Twenty individual aptamer sequences were characterized using confocal fluorescence microscopy and flow cytometry analysis, and 14 of them had targeting to more than 70% of L. infantum promastigotes with different subcellular localization patterns. Subsequent dot blot analyses narrowed down the selection to five candidates for further characterization through an aptamer-linked immobilized sorbent assay where it was possible to detect endogenous LiGP63 in L. infantum promastigote lysates. The five selected aptamers recognized the recombinant LiGP63 protein with binding affinities ranging from 0.3 to 2.1 µM. Promastigotes preincubated with LiGP63Apt-4, -27 and -28 exhibited a significantly reduced adhesion to and infection of RAW 264.7 macrophages. Moreover, when LiGP63Apt-4 and -28 were conjugated to liposomes, these two aptamers significantly enhanced the targeting to L. infantum promastigotes compared to plain liposomes. Conclusions: Given their improved stability and cost-effectiveness over antibodies, the aptamers evolved here represent promising candidates for new therapeutic and diagnostic approaches and for future nanoparticle-based drug delivery strategies in leishmaniasis. Full article

(1) Background: This study evaluates the anticancer potential of a newly synthesized azomethine-based compound, 6,6′,5,8-Dioxa-2,11-diazadodeca-1,11-diene-1,12-diyl)bis(4-bromo-2-methoxyphenol) (B-134-0), against osteosarcoma (SAOS-2) cells, focusing on its effects on apoptosis and DNA-damage-related gene expression. (2) Methods: B-134-0 was synthesized via condensation and tested at eight concentrations (0.5–100 μg/mL) for 24, 48, and 72 h. Cytotoxicity was assessed through MTT assay, and gene expression levels of TP53, RAD51, BRCA2, CASP2, MYC, MDM2, CDKN1A, ERCC1, ATR, and PRKDC were quantified through qPCR using the ΔΔ_Ct method. Molecular docking and DFT analyses were performed to explore structural stability and protein interactions. (3) Results: B-134-0 exhibited strong time-dependent cytotoxicity (IC₅₀: 71.58, 54.36, and 12.59 μg/mL at 24, 48, and 72 h, respectively) and significantly modulated the expression of cell cycle and DNA-repair-associated genes. The compound notably downregulated TP53, RAD51, CASP2, MYC, and MDM2, while CDKN1A and BRCA2 showed relative upregulation, indicating activation of the DNA damage response. Docking results revealed strong binding affinity with BRCA2 and CDKN1A, consistent with experimental findings. (4) Conclusions: These results indicate that B-134-0 exhibits potent anticancer activity by modulating DDR and apoptosis pathways, with strong molecular stability, suggesting its promise as a therapeutic candidate for osteosarcoma. Full article

Three novel metal complexes of the tridentate ligand 4-nitro-2-(quinolin-8-yliminomethyl)phenol (NQP) were synthesized and fully characterized using elemental analysis, TGA, magnetic susceptibility, FT-IR, NMR, and UV–Vis spectroscopy. Stoichiometric studies and characterization data proposed square-planar Pd(II), tetrahedral Zn(II), and octahedral Fe(III) geometries. Density functional theory calculations (B3LYP and B3LYP/6-311G(d,p) with LANL2DZ for metals) showed good agreement with experimental findings and revealed enhanced nonlinear optical properties, as evidenced by increased polarizability and hyperpolarizability values. Biological studies demonstrated significant antimicrobial activity, with the Pd–NQP complex exhibiting superior efficacy against bacterial and fungal strains compared to ofloxacin and fluconazole, following the order NQP < Zn < Fe < Pd. Cytotoxicity assays against Hep-G2, MCF-7, and HCT-116 cell lines revealed strong anticancer activity, particularly for the Pd(II) complex (IC₅₀ = 6.35–12.95 μ_g/μL), comparable to cisplatin. All complexes showed higher DPPH radical scavenging activity than ascorbic acid and strong DNA-binding affinity. Antimicrobial activity was further validated experimentally, while molecular docking studies elucidated favorable binding interactions with microbial proteins and cancer-related targets. Full article

Aptamers are powerful tools for detecting and analyzing biomolecules that consist of proteins or nucleic acids. However, their application to aptamers against viroids—highly structured self-replicating RNAs—has not yet been explored. In this study, a magnetic bead- and high-throughput sequencing-based SELEX (MB-HTS-SELEX) protocol for selecting potential aptamers against potato spindle tuber viroid (PSTVd) is presented. Full-length biotinylated-PSTVd RNA was transcribed in vitro, immobilized on streptavidin-coated magnetic beads, and incubated with a library of ~3.32 × 10¹⁴ molecules of random single-stranded oligo-DNAs (oligo-ssDNAs) of 20, 30, or 40 nucleotides (L20, L30, or L40, respectively) flanked by primer binding sites for downstream PCR amplification. Simultaneous biotin labeling of the anti-aptamer strand of the resulting double-stranded DNA (dsDNA) amplicons facilitated strand separation using streptavidin-coated magnetic beads. After 10 selection rounds, high-throughput sequencing, followed by bioinformatics analysis of the generated sequences, allowed for the detection of several enriched sequences, representing putative PSTVd-binding aptamers. Subsequent pull-down assays showed that the most abundant oligo-ssDNA in L30 was docked on PSTVd molecules. This combination method may ameliorate the selection of high-affinity aptamers against PSTVd, reduce the number of selection cycles, time, and other costs of aptamer production, thereby promoting future massive and cost-effective viroid detection and characterization. Full article

This study compares the chemical composition, antimicrobial effects, and antibiotic-potentiating capacity of three Lauraceae essential oils (EO): Cryptocarya agathophylla (CAEO), Litsea cubeba (LCEO), and Laurus nobilis (LNEO). Gas chromatography–mass spectrometry (GC–MS) analysis revealed distinct chemotypes: CAEO and LCEO were dominated by oxygenated monoterpenes, while LNEO contained the highest levels of monoterpene hydrocarbons. Antibacterial testing against nine bacterial strains showed strain-dependent growth suppression trends, while true minimum inhibitory concentrations (MICs) were reached only in selected cases. EO–ampicillin interactions were evaluated using MIC-based checkerboard criteria, whereas OD-derived inhibition parameters were used exclusively to describe sub-MIC potentiation trends. In combination assays, LNEO exhibited the most pronounced potentiating effects against Streptococcus pyogenes, Shigella flexneri, and Haemophilus influenzae, while CAEO and LCEO showed moderate or strain-dependent enhancement. Hierarchical clustering highlighted distinct oil- and strain-specific interaction profiles. Overall, although CAEO displayed stronger intrinsic antibacterial effects when tested alone, LNEO emerged as the most effective potentiator of ampicillin activity in a strain-dependent manner. The effects of the major compounds identified in the Lauraceae EO were assessed in silico against protein targets of some microorganisms using the AutoDock software version 4.2.6. The docking scores revealed binding affinities of the bioactive compounds towards Dpr protein (4.3–5.8 kcal/mol), DNA gyrase (4.7–7.1 kcal/mol), mono- diacylglycerol lipase (4.4–6.2 kcal/mol), CYP51 (5.8–8.0 kcal/mol), phage-encoded quorum sensing anti-activator (5.8–8.0 kcal/mol) and Chondroitin ABC lyase I (4.8–6.3 kcal/mol). Two (2) hit compounds (α-Citral, β-Citral) were finely defined by strong hydrophobic and hydrophilic interactions with the bacterial and fungal protein targets, respectively. Full article