Chemistry & Biodiversity最新文献

The present work describes the synthesis of new 1,2,4-triazole derivatives incorporating an amide moiety, obtained through a reaction sequence involving amidation, cyclization, and alkylation steps. Structural characterization of the synthesized 1,2,4-triazole–amide conjugates was confirmed by nuclear magnetic resonance (¹H, ¹³C) and high-resolution mass spectrometry analyses. The antimicrobial evaluation revealed significant activity, particularly against fungal strains such as Candida albicans, Aspergillus flavus, and Fusarium oxysporum, with minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) values ranging from 5 to 20 µg/mL, and the most active compounds, 3d and 3c, showed MIC = 5 µg/mL and MFC = 10 µg/mL. Docking analysis further demonstrated favorable interactions of all derivatives with lanosterol 14-α-demethylase (CYP51), with compound 3d exhibiting the highest binding affinity (−9.6 kcal/mol). Molecular dynamics simulations confirmed the stability of the 3d-CYP51 complex (root mean square deviation < 2.5 Å over 100 ns). Absorption, Distribution, Metabolism, Excretion, and Toxicity predictions and drug-likeness assessments additionally indicated that the synthesized molecules possess acceptable pharmacokinetic properties, supporting their potential as antimicrobial agents.

This study aims to evaluate the potential effects of Omphalodes cappadocica on a breast cancer cell line for the first time. The methanol extract of the aerial parts (Ae-M) exhibited the strongest cytotoxicity against MCF-7 and MDA-MB-231 cells after 48 h of incubation, with IC₅₀ values of 14.08 ± 0.05 and 10.63 ± 0.01 µg/mL, respectively. The root methanol extract (Ro-M) exhibited significant activity in the MCF-7 and MDA-MB-231 cell lines during 48 h of incubation, with IC₅₀ values of 19.25 ± 0.66 and 16.38 ± 0.02 µg/mL, respectively. Quantitative analysis by LC–MS/MS revealed that the main constituents of Ae-M were rosmarinic, quinic, and vanillic acids. Quinic and fumaric acids were identified in Ro-M. Quinic acid had a strong affinity for the target proteins PDB 3ERT, PDB 3HNG, and PDB 3KMU, with docking scores of −9.2, −7.8, and −6.6 kcal/mol, respectively. The docking score for rosmarinic acid for the target protein PDB 3HNG was determined to be −9.7 kcal/mol. The findings suggest that O. cappadocica may serve as a source for the development of anticancer agents.

Foeniculum vulgare was investigated for the comparative phytochemical profiles and bioactivities of its aqueous extracts (decoction, E1; Soxhlet, E2) and essential oil (EO), together with in silico exploration of major constituents. Phenolics, flavonoids, and tannins were quantified spectrophotometrically, individual metabolites profiled by HPLC/UV–ESI–MS, and volatile components by GC–MS. Antioxidant capacity (DPPH, FRAP, TAC), antimicrobial activity (MIC/MBC or MFC against 29 bacteria and 8 fungi), and anticoagulant effects (prothrombin time [PT] and activated partial thromboplastin time [aPTT]) were assessed. Molecular docking targeted β-lactamases (OXA-10), thrombin, and myeloperoxidase. The decoction (E1) showed the highest phenolic (56.8 mg GAE/g) and flavonoid (22.8 mg QE/g) contents and superior radical-scavenging activity (DPPH IC₅₀ = 228.8 µg/mL). The EO was dominated by (E)-anethole (79.7%) and fenchone (7.7%). The aqueous extract is rich in phenolic acids and flavonoids (quercetin-3-glucuronide 12.13%, chlorogenic acid 10.63%), typifying a caffeoylquinic acid–glucuronidated flavonol chemotype. Antimicrobial testing showed that the aqueous extract stopped Acinetobacter baumannii from growing (MIC = 600 µg/mL) and the EO stopped Candida parapsilosis from growing (MIC = 1200 µg/mL). E1 extended the aPTT to 73.7 s compared to 34.6 s in the control group, indicating disruption of the intrinsic coagulation pathway, whereas PT exhibited minimal alteration. Docking studies revealed that quercetin-3-glucuronide demonstrates significant binding affinity to β-lactamase OXA-10 (−6.4 kcal/mol) and thrombin (−7.4 kcal/mol), thereby substantiating its proposed roles in antibacterial and anticoagulant activities. In general, F. vulgare aqueous extracts and EO have antioxidant, antimicrobial, and anticoagulant properties that work well together. Phenolic glycosides and (E)-anethole are the main ingredients that make this happen. These results bolster translational opportunities for the development of cardiovascular, antimicrobial, and nutraceutical adjuncts, while emphasising the necessity for in vivo validation, bioavailability investigations, and long-term safety evaluations.

Lasioderma serricorne is a prevalent stored-product pest that infests various grains and processed foods. The overuse of synthetic insecticides has led to insecticide resistance and environmental contamination. Plant essential oils (EOs) have emerged as a promising eco-friendly alternative. The present research extracted EOs from Citrus reticulata different parts (fruit peel, flower, branch, and leaf) and collected leaf EOs at different extraction times via hydrodistillation. Peel EO was dominated by d‑limonene (98.13%), whereas flower EO contained d‑limonene (30.56%) and 3-carene (22.23%) as major components. In leaf and branch EOs, γ‑terpinene was the primary component (56.63% and 28.09%, respectively). Peel EO exhibited the strongest contact toxicity (LD₅₀ = 8.23 mg/L air). For leaf EOs collected in segments, their contact toxicity increased with extraction time, with EO extracted during the fourth time segment (CRL-4) showing the highest activity (LD₅₀ = 8.65 mg/L air). The third time-segment leaf oil (CRL-3) demonstrated excellent repellent activity and persistence, maintaining a consistently high repellency rate of 96% after both 2 and 4 h of exposure. Overall, our study was the first to report the insecticidal and repellent effects of C. reticulata EO against L. serricorne; these findings demonstrated that C. reticulata EOs can serve as eco-friendly alternatives to synthetic insecticides.

The manuscript describes the explorations on [4+2] cycloaddition of newly in situ generated 3-(allyl/propargyl-thio)propanone as 2π-components with functionalized 1,3-diazabuta-1,3-dienes as 4π-components for the synthesis of 5-allyl/propargyl-thio methyl pyrimidinones. The synthetic methodology is simple to operate, mild, and successful with a wide range of functionalized 1,3-diazabuta-1,3-dienes in the development of functionalized pyrimidinones. The synthesis of these functionalized pyrimidinones is significant as functionalized pyrimidinones have diverse pharmacological relevance and are useful synthons for the synthesis of condensed heterocycles.

The continuous emergence of novel psychoactive substances (NPS) poses significant challenges to drug discovery, regulation, and public health. In this study, a computational chemometric approach was applied to evaluate 134 opioids belonging to the NPS class using ACD/Percepta software. Parameters that were predicted are physicochemical characteristics, ADME (Absorption, Distribution, Metabolism, and Excretion) profiles, and toxicity endpoints. Data pre-processing involved standardization, outlier detection via Grubbs’ test, and distribution assessment using the Kolmogorov–Smirnov test. Multivariate statistical analyses (MANOVA, discriminant analysis, and principal component analysis) revealed significant correlations between Lipinski and lead-likeness violations and parameters such as log P, molecular weight, solubility, protein binding, blood–brain barrier penetration, metabolic stability, P-glycoprotein interaction, and cytochrome P450 inhibition. Discriminant analysis achieved up to 100% classification accuracy for certain parameter combinations, suggesting that log P and molecular weight alone can reliably predict broader ADMET (Absorption, Distribution, Metabolism, Excretion, and Toxicity) profiles. These results demonstrate the utility of integrating in silico prediction platforms with chemometric methods to prioritize candidate compounds for further experimental evaluation, thereby supporting efficient lead selection within the opioid NPS class.

In this study, a green and efficient method has been developed for the preparation of aryl semicarbazones using Kigelia pinnata flower-derived carbon quantum dots (KP-CQDs) as a sustainable catalyst. The reaction between various aldehydes/acetophenones and semicarbazide (SC) hydrochloride was carried out smoothly at room temperature in an ethanol–water (1:4) solvent system, and excellent yields (83%–95%) were achieved within a short reaction time of 5–20 min, demonstrating the high catalytic efficiency of KP-CQDs. A total of nine derivatives were synthesized, among which six compounds are reported for the first time. Furthermore, the biological potential of these compounds was investigated through in silico studies. The molecules were subjected to prediction of activity spectra for substances (PASS) online prediction to predict probable biological targets, and based on these predictions, molecular docking was performed against human mitochondrial 3-hydroxy-3-methylglutaryl-coenzyme A synthase 2 (Protein Data Bank [PDB] ID: 2WYA), hepatitis A virus 3C protease (PDB ID: 1HAV), and foot-and-mouth disease virus (FMDV) 3C protease (PDB ID: 2WV4). On conducting molecular docking, molecules 3f (−15.57 kcal/mol), 3c (−5.61 kcal/mol), and 3e (−9.44 kcal/mol) showed remarkable activity with 2WYA, 1HAV, and 2WV4, respectively. This method offers several key advantages, including the use of a green and reusable CQD catalyst, mild reaction conditions, short reaction times, excellent yields, and the preparation of new semicarbazone derivatives with unexplored biological activities.

Piper longum Linn., or long pepper, is an important medicinal plant in Ayurveda known for its anti-inflammatory, antioxidant, and bio-enhancing properties. Its phytochemical composition, particularly piperine (PP) and piperlongumine (PLG), is affected by its cultivation in different geographical locations. Understanding these geographical variations is essential for optimizing its medicinal use and ensuring quality in herbal formulations. This study investigates the impact of geographical variation on the phytochemical and pharmacognostical properties of P. longum Linn, an essential Ayurvedic medicinal plant. Samples were collected from three distinct regions in India—Ranikhet, Western Ghats-Kerala, and Bangalore—to evaluate differences in the concentration of vital bioactive compounds, PP and PLG. Pharmacognostic, physicochemical, and phytochemical analyses were conducted using standard methods. Reverse phase high-performance liquid chromatography (RP-HPLC) was used to measure the amount of markers, and 1,1-diphenyl-2-picryl hydrazyl (DPPH) assays were used to calculate the antioxidant activity. The results reveal significant differences in bioactive marker concentrations across the regions, with the Ranikhet sample showing the highest levels of PP (12.57 ± 0.25 mg/g) and PLG (0.865 ± 0.012 mg/g), whereas the latter was absent in samples from the other regions. Additionally, the Ranikhet sample exhibited superior antioxidant activity and higher total phenolic and flavonoid content. Morphological differences were also observed in the plant fruits, varying in size and color across regions. According to these results, the location of P. longum affects its phytochemical makeup and antioxidant properties. This means that the Ranikhet region may be a better place to get it for making medicines that need PLG activity. This research highlights the importance of considering geographic origin in standardizing and sourcing medicinal plants for optimal therapeutic efficacy.

Benzylisoquinoline alkaloids (BIAs) are a diverse group of plant secondary metabolites with significant pharmacological activities, where methylation reactions catalyzed by methyltransferases play crucial roles in structural diversification and bioactivity modulation. In this study, we identified and functionally characterized two key methyltransferases, Sinomenium acutum 6-O-methyltransferase (Sa6OMT) and S. acutum coclaurine N-methyltransferase (SaCNMT), involved in BIA biosynthesis in S. acutum, a traditional Chinese medicinal plant with anti-rheumatoid arthritis properties. Candidate genes, including SaOMT3 and SaNMT4, were selected through transcriptome analysis of different tissues combined with phylogenetic analysis and expression pattern evaluation. Functional validation demonstrated that SaOMT3 encodes a 6OMT that catalyzes the conversion of (S)-norcoclaurine to (S)-coclaurine, while SaNMT4 encodes a CNMT that mediates the N-methylation of (S)-coclaurine to (S)-N-methylcoclaurine. Biochemical characterization revealed optimal activity at 40°C for both enzymes, with distinct optimal pH levels (8.5 for Sa6OMT and 8.0 for SaCNMT) and higher catalytic efficiency for SaCNMT. This study provides valuable insights into the molecular mechanisms underlying BIA biosynthesis in S. acutum and enhances our understanding of plant specialized metabolism.