Recent studies on Castanea sativa (C. sativa) leaves have primarily focused on limited phytochemical screening or single-target biological assays, leaving gaps in the comprehensive evaluation of their bioactive potential. This study aimed to systematically investigate the phytochemical composition, antioxidant capacity, multi-enzyme inhibitory activity, and molecular interaction profile of the methanolic extract of C. sativa leaves. UPLC-MS/MS analysis identified ellagic acid, chlorogenic acid, and quinic acid as major constituents, supported by high phenolic (190.556 mg GAE/g) and flavonoid (50.430 mg QE/g) contents. The extract exhibited strong antioxidant properties, particularly in cupric reducing antioxidant capacity (CUPRAC) and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid (ABTS• +) assays, demonstrating activities comparable to those of standard antioxidants. Notably, potent inhibitory effects were observed against carbonic anhydrase (CA) I-II, acetylcholinesterase (AChE) (IC50 = 0.0017 µg/mL), and α-glycosidase (IC50 = 0.0063 µg/mL), with AChE inhibition approaching that of tacrine and α-glycosidase inhibition surpassing acarbose by 2.3-fold. Molecular docking analyses further revealed specific interactions between major phytochemicals and enzyme active sites, supporting the in vitro findings. These results demonstrate that C. sativa leaves represent a promising, sustainable source of bioactive molecules with strong antioxidant and multi-target enzyme inhibition potential, suggesting possible applications in the management of oxidative stress-related conditions, neurodegenerative diseases, and metabolic disorders such as diabetes.

Background/Objectives: Lavandula cariensis species is cultivated uncommonly in the western region of Turkey. The colloquial appellations avayianos, karabasi, and myra are used to refer to the L. cariensis plant. The essential oil of L. cariensis was studied for its potential antiglaucoma, antioxidant, antidiabetic, and acetylcholinesterase inhibitory effects. Methods: The inhibitory effect of the essential oil of L. cariensis on the acetylcholinesterase (AChE), carbonic anhydrase II (CA II), and α-amylase enzymes was determined. Therefore, chemical profiles of L. cariensis’ essential oil were identified using Gas Chromatography Mass Spectrometry (GC-MS) and as Chromatography with Flame Ionization Detection (GC-FID) analyses. Results: Camphor (39.73%), fenchone (19.49%), exobornyl acetate (6.81%), camphene (5.49%), and eucalyptol (5.49%) were the most abundant compounds in L. cariensis essential oil. Radical scavenging effect of the essential oil of L. cariensis was examined using 1,1-diphenyl-2-picrylhydrazyl (DPPH) (IC50: 231.0 ± 0.094 μg/mL) and 2,2′-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS) (IC50: 7.45 ± 0.013 μg/mL) radicals. Also, the ferric ions (Fe3+), cupric ions (Cu2+), and Fe3+-2,4,6-tri(2-pyridyl)-S-triazine (TPTZ) complex reducing capabilities were studied. Additionally, essential oil of L. cariensis indicated a comparable level of inhibition towards hCA II (IC50: 276.42 μg/mL), AChE (IC50: 14.22 μg/mL), and α-amylase (IC50: 475.63 μg/mL) enzymes. Conclusions: The evaluation of the antioxidant capabilities and enzyme inhibition profiling of the essential oil of L. cariensis will be made possible by this comprehensive study, which serves as a springboard for further research. The essential oil of L. cariensis demonstrated enzyme-inhibitory activities against target enzymes associated with Alzheimer’s disease, diabetes, and glaucoma. Also, this study’s in vitro inhibition suggests promising prospects.

Anthocyanins are water-soluble plant pigments. They give many plants, fruits, vegetables, and cereal kernels their red, purple, and blue colors. This research aims to reveal the biological properties of peonidin as an anthocyanin. To comprehend the antioxidant capabilities of peonidin, 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) radical (ABTS•+), N,N-dimethyl-p-phenylenediamine dihydrochloride radical (DMPD•+), and 1,1-diphenyl-2-picrylhydrazyl free radical (DPPH•) scavenging, Fe3+-2,4,6-tris(2-pyridyl)-s-triazine (TPTZ), and Cu2+ reducing assays were recorded. The IC50 values for peonidin against ABTS•+, DMPD•+ and DPPH• scavenging capabilities were determined to compare with standard antioxidants. ABTS•+ radical scavenging activity of peonidin had an IC50 value of 15.40 μg/mL, while the IC50 values for BHA, BHT, Trolox, and α-Tocopherol were 12.82, 11.78, 12.67, and 10.83 μg/mL, respectively. DPPH radical scavenging activity of peonidin had an IC50 value of 41.63 μg/mL, while the IC50 values for BHA, BHT, Trolox, and α-Tocopherol were 8.45, 23.10, 6.30, and 18.73 μg/mL, respectively. Enzyme inhibition was studied to investigate the effects of peonidin. The Ki values of peonidin were 114.33, 63.02, 2.99, 9.76, and 15.14 nM toward hCA I, hCA II, AChE, BChE, and α-glycosidase enzymes, respectively. Furthermore, peonidin’s interactions with target enzymes BChE, hCA I, hCA II, AChE, and α-glycosidase were investigated by molecular docking. The results suggest that antioxidant-rich peonidin is a plant-based compound with potential use in the treatment of glaucoma, Alzheimer’s disease, and diabetes.

This study investigated the chemical composition of the essential oil (EO) and the phenolic profiles of methanol extracts from Satureja boissieri Hausskn. ex Boiss. EO analysis by Gas Chromatography-Mass Spectrometry (GC-MS) identified carvacrol (45.2%), cymene (26.0%) and γ-terpinene (17.5%) as the primary constituents. Phenolic profiles were quantified via Liquid Chromatography-High-Resolution Mass Spectrometry (LC-HRMS), revealing syringic acid (56,647.96 mg/kg extract), rosmarinic acid (47,777.98 mg/kg extract) and hesperidin (6353.49 mg/kg extract) as major components in the extract. The antioxidant potential was evaluated through three distinct radical scavenging assays (DPPH, ABTS and DMPD) and the determination of ferric (Fe3+) and cupric (Cu2+) reducing capacities. Notably, S. boissieri exhibited potent antioxidant activity, with IC50 values of 11.74 µg/mL for DPPH and 9.90 µg/mL for ABTS radical scavenging, demonstrating performance comparable to standard antioxidants such as α-tocopherol (11.31 and 8.37 µg/mL, respectively). Furthermore, the in vitro inhibitory activities against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes were evaluated. While both extracts exhibited similar and significant AChE inhibition (35.3% and 32.4%, respectively), the essential oil was notably more potent against BChE than the methanol extract. These findings suggest that S. boissieri is a significant source of bioactive compounds with promising antioxidant and neuroprotective potential for pharmaceutical applications.

Uracil-appended organic ligands are interesting molecules in terms of enzyme inhibition studies as a result of their multifunctional structures. Herein, a series of novel 1,2,3-triazole substituted 5-arylideneuracils were obtained via click chemistry in a two-step procedure with moderate to good yields (28-67% yields). All of the compounds were characterized using Fourier transform infrared spectroscopy (FT-IR), proton and carbon nuclear magnetic resonance spectroscopy (1H and 13C NMR) and high resolution mass spectrometry (HR-MS). The inhibition abilities of novel 5-arylideneuracils (2a-2j) were evaluated against acetylcholinesterase (AChE) and human carbonic anhydrase I and II (hCA I and II) isoenzymes which are mainly associated with some global disorders such as Alzheimer's disease (AD), diabetes, epilepsy, and glaucoma. The compounds exhibited inhibition profiles with Ki values ranging from 4.21+1.51 nM to 52.79+10.58 nM for AChE, 130.80+34.34-410.40 +32.44 nM for hCA I and 64.25 + 7.62-614.40+98.45 for hCA II. Tacrine was used as a reference inhibitor for AChE and exhibited a Ki value of 2.59+0.91 nM against the AChE enzyme. On the other hand, Acetazolamide was used as a standard inhibitor towards hCA I and hCA II isoforms with Ki values of 81.0 + 14.0 nM and 258.0 + 92.0 nM, respectively. The inhibition results related to key metabolic and neurological enzymes suggest that novel 5-arylideneuracils may serve as promising candidates for the development of new drugs targeting global diseases such as Alzheimer's disease (AD), glaucoma, and epilepsy. To elucidate the binding interactions of these compounds with AChE, hCA I, and hCA II, molecular docking simulations were performed. Compound 2i has shown superior activity in vitro and in both docking and molecular dynamics simulations, indicating its potential as a promising alternative to tacrine for AChE inhibition.

Coniferyl alcohol and coniferyl aldehyde are precursors of lignin and are used in spices and the pharmaceutical industry. In this work, antioxidant, anticholinergic, antidiabetic, and antiglaucoma effects of coniferyl alcohol and aldehyde were evaluated and compared against the standards. To determine the antioxidant capacities of coniferyl alcohol and aldehyde, ABTS center dot+, DMPD center dot+ and DPPH center dot scavenging abilities as well as cupric ion (Cu2+) reduction, ferrous ions (Fe2+) reduction and Fe3+-TPTZ reduction activities were studied. Butylated hydroxytoluene (BHT), ascorbic acid, alpha-Tocopherol, Trolox, and butylated hydroxyanisole (BHA) were used as the standard antioxidants. When the antioxidant effects of coniferyl alcohol and coniferyl aldehyde are compared to the standards, they exhibit significant antioxidant effects. In addition, it was determined that coniferyl alcohol and coniferyl aldehyde had a high degree of inhibition effect towards carbonic anhydrase (hCA) I and II isoforms purified from human erythrocytes, alpha-glycosidase, butyrylcholinesterase (BChE), acetylcholinesterase (AChE), and alpha-amylase as in vitro and in silico. Molecular docking studies revealed favorable binding affinities of coniferyl alcohol and coniferyl aldehyde toward all investigated enzymes, with key hydrogen bonding and pi-pi interactions identified at the active sites. The docking findings were found to be compatible with the in vitro enzyme inhibition results, supporting the proposed multi-target biological potential of both compounds. Molecular docking studies revealed favorable binding affinities of coniferyl alcohol and coniferyl aldehyde toward all investigated enzymes. Key hydrogen bonding and pi-pi interactions were identified within the active sites, particularly for AChE and hCA II. The docking results were consistent with the in vitro enzyme inhibition data, supporting their multi-target biological potential. Docking demonstrated that both compounds can effectively interact with the catalytic regions of the target enzymes. The identified binding modes and interaction patterns support the observed inhibitory activities and provide a molecular basis for their multi-target biological effects.

Brassicaceae plants, among the most widely consumed vegetables worldwide, are recognized as rich sources of biologically active compounds. In this study, nine species belonging to the cruciferous genus Thlaspi were investigated, including T. alliaceum, T. arvense, T. violascens, T. aghricum, T. cataonicum, T. annuum, T. watsonii, T. cariense, and T. elegans. In the past, pennycress species were consumed to alleviate hunger and provide nutritional support during periods of food scarcity. To evaluate the antioxidant capacities of methanol and water extracts obtained from Thlaspi species, several complementary assays were employed, including 2,2′-azino-bis-3-ethylbenzthiazoline-6-sulphonic acid radical (ABTS•+) scavenging, 1,1-diphenyl-2-picrylhydrazyl free radicals (DPPH•) scavenging, N,N-dimethylphenylenediamine radicals (DMPD•+) scavenging, Fe3+-2,4,6-tris(2-pyridyl)-s-triazine (TPTZ)-reducing, Fe3+ ion-reducing, and Cu2+ ion-reducing assays. The IC50 values of both methanol and water extracts from the aerial parts of Thlaspi species for ABTS•+, DPPH•, and DMPD•+ scavenging activities were studied compared with antioxidant standards, including α-tocopherol, Trolox, butylated hydroxytoluene (BHA), and butylated hydroxyanisole (BHT). The total phenolic and flavonoid contents of the extracts ranged from 8.29 to 49.14 mg gallic acid equivalent (GAE)/g extract and from 2.33 to 74.66 mg quercetin equivalent (QE)/g extract, respectively. Furthermore, the inhibitory effects of water and methanol extracts of Thlaspi species against α-amylase, acetylcholinesterase (AChE), and carbonic anhydrase (CA II) enzymes were evaluated. The IC50 values were determined to range from 122.4 to 245.9 μg/mL for α-amylase, from 17.3 to 24.1 μg/mL for AChE, and from 41.9 to 256.5 μg/mL for CA II inhibition. In addition, the phenolic profiles of Thlaspi species were comprehensively characterized by LC-MS/MS analysis using 53 reference standards. The findings demonstrated that the aerial parts of Thlaspi species are rich in polyphenolic antioxidants and may serve as promising natural sources with potential applications in the management of diabetes, Alzheimer’s disease (AD), glaucoma, epilepsy, and cancer.

The antioxidant activity of polyphenolic scaffolds and the selectivity of enzyme inhibition can be significantly modified through structural modification. The antioxidant properties and the multi-target enzyme inhibitory properties of resveratrol and three structurally different analogs (oxyresveratrol, 3′,5′-dimethoxyresveratrol and triacetylresveratrol) were comparatively assessed to clarify the structure-activity relationships. The antioxidant activity was measured using complementary electron-transfer assay, radical-scavenging assay, and metal chelating assay, whereas the enzyme inhibition was evaluated against hCA I and hCA II, GST, AChE, BChE, and α-glycosidase, as well as α-amylase enzymes. Oxyresveratrol showed the best antioxidant behavior in most of the assays, which is in line with the occurrence of the extra additional hydroxyl groups, which increases the ability to donate electrons. Conversely, acetylation significantly minimized radical scavenging action and enhanced enzyme inhibition abilities. The strongest inhibitory activity of triacetylresveratrol was exhibited against hCA I (IC50: 49.50 nM), hCA II (IC50: 46.50 nM), BChE (IC50: 46.20 nM), and against α-glycosidase, whereas, 3′,5′-dimethoxyresveratrol showed the strongest inhibition ability against AChE (IC50: 13.86 nM). Comparatively, resveratrol exhibited a relatively high GST inhibition (IC50: 463.54 nM), which showed the role of the free phenolic groups in the enzyme interaction. These results reveal that hydroxylation positively impacts the antioxidant activity, but acetylation and methoxylation regulate selectivity and the enzymes inhibition potency. The observed differences in biological profiles between the derivatives provide mechanistic insight of activity changes based on functional groups and the selection of resveratrol multi-target therapeutic derivatives in oxidative stress-linked and metabolic diseases.

This study investigates the antioxidant, enzyme inhibitory, and antimicrobial activities of water (WEHL) and ethanol (EEHL) extracts of hop (Humulus lupulus) cones. Phytochemical analyses revealed higher total phenolic content in EEHL (271.52 +/- 0.13 mg GAE/g) than in WEHL (251.84 +/- 0.06 mg GAE/g), as well as higher total flavonoid content (182.56 +/- 0.45 mg QE/g for EEHL versus 179.39 +/- 0.46 mg QE/g for WEHL). Antioxidant activity, determined by DPPH and ABTS assays, showed that EEHL had stronger radical scavenging capacity with IC50 values of 19.13 +/- 4.66 mu g/mL (DPPH) and 12.66 +/- 1.94 mu g/mL (ABTS), compared to WEHL (DPPH: 20.90 +/- 2.39 mu g/mL; ABTS: 32.41 +/- 4.29 mu g/mL). In reducing assays, EEHL also showed better absorbance values in FRAP (0.77 +/- 0.01), CUPRAC (2.09 +/- 0.05), and Fe3+ reducing (1.95 +/- 0.01) tests. EEHL likely outperformed WEHL due to solvent polarity and extraction efficiency. Moderately polar ethanol extracts a broader range of phenolics and flavonoids, including fewer polar bioactive compounds that contribute to antioxidant capacity and enzyme inhibition. This matches higher TPC/TFC in EEHL and explains stronger radical scavenging, reducing power, and multi-enzyme inhibition. Enzyme inhibition studies revealed that EEHL inhibited acetylcholinesterase (IC50: 26.06 mu g/mL), butyrylcholinesterase (IC50: 44.00 mu g/mL), alpha-glycosidase (IC50: 119.31 mu g/mL), and carbonic anhydrase isoenzymes hCA I (IC50: 59.78 mu g/mL) and hCA II (IC50: 21.19 mu g/mL). LC-MS/MS analysis identified major phenolic compounds such as isoquercitrin (3.14 ng/mL), rutin (0.60 ng/mL), and hesperidin (0.43 ng/mL) in EEHL. Antimicrobial screening showed selective activity against Staphylococcus aureus with an inhibition zone of 18.50 +/- 0.58 mm, while no inhibition was observed against Escherichia coli and Candida albicans. These findings provide a solvent-dependent in vitro profile that can guide extraction strategies, support antioxidant and multi-enzyme screening (including hCA I and II), and identify candidates for selective antimicrobial evaluation and further preclinical investigation. Despite extensive use of hop extracts, comparative solvent-dependent profiling that links LC-MS/MS phenolic composition with a broad multi-enzyme inhibition panel, including the less frequently evaluated hCA I/II isoenzymes, remains limited. Therefore, the objective of this study was to systematically compare WEHL and EEHL in terms of phytochemical content and in vitro antioxidant, enzyme inhibitory, and antimicrobial activities. Overall, these results provide a solvent-dependent, comparative in vitro profile of WEHL vs. EEHL that can support antioxidant, multi-enzyme screening (including hCA I and II), and selective antimicrobial assays.

This study presents the synthesis of acetyl-and fluorinated group-containing imidazol-2-ylidene silver complexes. The structures of the complexes obtained via deprotonation method were elucidated using spectroscopic techniques such as NMR, FTIR, and MS, as well as elemental analysis. In addition, the enzyme inhibition profiles of the synthesized Ag(I)-NHC complexes were thoroughly investigated against human carbonic anhydrase isoforms I and II (hCAs I and II), as well as acetylcholinesterase (AChE). Notably, compound 2f, bearing 2-chloro and 4-fluoro groups, exhibited superior inhibition potency against hCA I and AChE enzymes, with Ki values outperforming the reference inhibitors acetazolamide (AZA) and tacrine (TAC). These findings suggest that the dual halogenation pattern enhances both electrostatic and hydrophobic interactions within enzyme active sites. In addition, the cytotoxic activity of compound 2f was determined using MTT assays in SH-SY5Y (neuroblastoma), HCT-116 (colorectal carcinoma), and MCF-7 (breast adenocarcinoma) cell lines, yielding IC50 values of 35.63 +/- 0.84 mu M, 49.37 +/- 0.97 mu M, and 54.92 +/- 1.94 mu M, respectively. Further, we examined the inhibition potential of three most potent compounds (2a, 2e and 2f) with in silico molecular docking with three target proteins (hCA I, hCA II, and AChE). The binding energy score and ligand-protein interactions were indicating excellent inhibition potential of examined compounds. Overall, these results highlight the multi-target enzyme-blocking ability of 2f as a promising candidate for suppressing tumor growth.

In the context of research into known synthetic possibilities under the conditions of condensation reaction, based on cobalt salt (Co(CH3COO)2•4H2O) with 3-((1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1 H-pyrazol-4-yl)diazenyl)pentane-2,4-dione, metal-complex was synthesized. To assess its interactions with biological targets, a single-crystal X-ray diffraction structure analysis were conducted. It has been revealed that independent part of the unit cell of the cobalt(II) complex contains one complex molecule of composition C32H34N8O6Co(II), one molecule of acetic acid anion and five molecules of water of crystallization. All atoms are in a general position. The four O atoms in the equatorial plane around the Co atom form a slightly distorted square-planar arrangement with an average Co-O bond length of 1.888 Å, and the slightly distorted octahedral coordination is completed by the two N atoms of the in the axial positions. Each Co(II)-complexes contain two independent molecules of C16H17N4O3. This molecule has pentagonal and hexagonal cyclic fragments. This complex is effective inhibitor of the α-glycosidase, butyrylcholinesterase (BChE), cytosolic carbonic anhydrase I and II isoforms (hCA I and II), and acetylcholinesterase enzymes (AChE) with Ki values of 1.93 ± 0.38 µM for hCA I, 1.85 ± 0.12 µM for hCA II, 6.31 ± 0.47 µM for α-glycosidase, 39.54 ± 8.18 µM for BChE, and 49.85 ± 15.72 µM for AChE, respectively. Afterwards, the interactions of the molecules against various proteins that are structure of α-galactosidase (α-Gly) (PDB ID: 1R47), carbonic anhydrase I (hCA I) (PDB ID: 2CAB), carbonic anhydrase II (hCA II) (PDB ID: 3DC3), acetylcholinesterase (AChE) (PDB ID: 4M0E), and butyrylcholinesterase (BChE) (PDB ID: 5NN0) were examined and their activities were compared.

The growing interest in natural product research as a safer and sustainable alternative to synthetic drugs has triggered this study, which evaluates the chemical profile and biological activity of Orobanche racemosa extracts. In the current study, extraction was performed from O. racemosa using the maceration method with several extraction solvents. The extracts were examined for their antioxidant and enzyme‐inhibitory activities and their effects on cell viability. In high‐performance liquid chromatography–MS/MS analysis, a total of 31 compounds was detected across all studied extracts. The EtOH and EtOH/water extracts consistently exhibited the highest antioxidant capacities in almost all tested assays. Similarly, EtOH and EtOH/water extracts showed vigorous anti‐AChE activity, measuring 2.88 and 2.35 mg/GALAE, respectively. In the cell viability assay, both EA and EtOH extracts of O. racemosa demonstrated potent cytotoxicity, significantly reducing viability in normal (HEK293) and cancer cell lines (HepG2, SH‐SY5Y), indicating high toxicity without selectivity. Molecular docking screened 384 theoretical compound–target combinations and retained 251 unique complexes with docking scores of −7.0 kcal/mol or lower after duplicated entries were removed. Subsequent single‐trajectory molecular dynamics analysis of seven representative high‐scoring complexes generated hypotheses regarding structural persistence under the simulated conditions; however, these computational predictions require experimental validation.

Schiff base transition-metal complexes are promising multifunctional scaffolds because metal coordination can regulate molecular geometry, electronic structure, and enzyme-binding behavior. This study aimed to synthesize pyrazolidine-based Cu(II) and Ni(II) complexes and clarify the role of metal coordination in their structural, theoretical, and multi-target enzyme inhibition profiles. The ligand and its Cu(II)-L and Ni(II)-L complexes were characterized by elemental analysis, FT-IR, UV–Vis, HPLC-PDA, and single-crystal X-ray diffraction, supported by Density functional theory (DFT), Quantum Theory of Atoms in Molecules (QTAIM), Hirshfeld surface analysis, and molecular docking/redocking. X-ray analysis revealed marked ligand reorganization after coordination, with Cu(II)-L showing a distorted coordination environment and Ni(II)-L a more symmetric square-planar geometry. DFT calculations gave HOMO–LUMO gaps of 1.78 eV for Cu(II)-L and 3.27 eV for Ni(II)-L, indicating higher reactivity for Cu(II)-L. Enzyme assays showed that Cu(II)-L was the most potent inhibitor of hCA I and AChE, with Ki values of 3.22 ± 0.60 μM and 4.78 ± 0.61 μM, respectively. Cu(II)-L and the free ligand exhibited comparable hCA II inhibition (4.50 ± 1.28 and 4.72 ± 1.35 μM), whereas the free ligand showed the strongest BChE inhibition (2.38 ± 0.10 μM). Docking results reproduced the experimental trends, with redocking RMSD values of 1.98, 1.96, 0.65, and 2.49 Å for hCA I, hCA II, AChE, and BChE, respectively. Overall, Cu(II) coordination enhances hCA I and AChE inhibition, while ligand flexibility favors BChE activity.

Hypericum ekerii Yüce and Aytaç, first described in 2017, remains poorly characterized in terms of its phytochemical composition and biological properties. This study investigated aerial-part extracts of H. ekerii prepared with ethyl acetate, acetone, 70% acetone-water, and water. The hydroacetone extract showed the highest total phenolic and flavonoid contents. LC/MS analysis enabled the annotation of 99 constituents, including phenolic acids, flavonoids, xanthones, anthraquinones, and acylphloroglucinols. The hydroacetone extract exhibited the strongest radical-scavenging and reducing activities, whereas acetone and ethyl acetate extracts showed the highest metal-chelating capacity. In enzyme assays, hydroacetone was the most active extract against acetylcholinesterase, tyrosinase, and hCA II, while ethyl acetate showed greater inhibition of butyrylcholinesterase and hCA I. The aqueous extract was the most active against α-glucosidase, and hydroacetone and ethyl acetate showed comparable α-amylase inhibition. Cytotoxicity remained limited overall; the lowest IC50 value was observed for the ethyl acetate extract against HCT-116 cells (95.09 µg mL-1), with weak selectivity (SI = 1.2). A QSAR-informed prioritization framework identified myricetin as the leading cross-layer candidate, p-coumaric acid as a target-specific priority metabolite, and ellagic acid, quercetin, and caffeic acid as antioxidant-priority candidates. Molecular docking supported favorable binding profiles for selected metabolites, while molecular dynamics simulations were used to assess the stability of representative complexes. Overall, H. ekerii appears to be a chemically diverse species with notable antioxidant and enzyme-inhibitory potential, providing a focused basis for future compound-level validation.

Because of the important biological properties of halogenated benzene sulfonamides, here we report the first synthesis of bromophenolic sulfonamides and their human carbonic anhydrase I (hCA I), human carbonic anhydrase II (hCA II) and acetylcholinesterase (AChE) inhibition. For this purpose, 4-bromo-1,2-dimethoxybenzene was reacted with chlorosulfonic acid fallowed by amination with ammonia, N-alkyl amines and N,N-dialkyl amines to give a series of novel sulfonamides. Subsequent O-demethylation of these sulfonamides using BBr3 afforded the target bromophenolic benzene sulfonamides. The synthesized bromophenolic sulfonamides were evaluated for their inhibitory effects against both hCA I/II and AChE enzymes. Among these compounds, 2-bromo-4,5-dihydroxy-N-phenylbenzenesulfonamide showed the strongest inhibition against hCA II (Kᵢ = 23.52 nM) and AChE (Kᵢ = 2.29 nM), exhibiting a 12.7 and 21.9-fold better inhibitory effect than the reference inhibitors acetazolamide (Kᵢ = 298.15 nM) and tacrine (Kᵢ = 50.21 nM), respectively. Similarly, N-benzyl-2-bromo-4,5-dihydroxybenzenesulfonamide displayed potent dual inhibition against hCA I (Kᵢ: 53.62 nM) and AChE (Kᵢ: 2.91 nM). In addition, the computational findings obtained from in silico induced fit docking, ADME prediction, and molecular dynamics (MD) simulations further supported and validated the experimental inhibition results.

Enzymes play important roles in various physiological processes, and dysregulation of enzyme expression is linked to the onset and progression of many diseases, including Alzheimer’s disease and diabetes. Enzyme-targeted therapies are promising in the treatment of enzyme-related diseases, making enzymes both biomarkers and targets for therapeutic investigations. In this study, the synthesis and biological assessment of novel multi-functionalized thiourea and thiazolidinone benzenesulfonamides were reported along with their CAs inhibition, AChE inhibition, α-glucosidase, and α-amylase inhibitions. While compound M1, which had a Ki value of 19.88 ± 1.04 nM (hCA I), was found to be the most potent hCA I inhibitor, compound M9, which had a Ki 8.9890 ± 0.8909 nM was found to be the strongest inhibitor against hCA II. Compound M1 showed remarkable AChE inhibition effects with a Ki value of 0.4740 ± 0.0818 nM in comparison to tacrine. The compounds showed Kis in the range of 4.9395 ± 0.8288 – 46.1207 ± 19.5197 nM against α-glycosidase and IC50 values in the range of 12.044 – 56.533 nM against α-amylase. In addition, molecular docking studies were performed to examine and evaluate the interaction of the lead compounds against the enzymes studied. The binding energy values and predicted inhibition constants (Ki) support the effectiveness of these molecules, aligning closely with experimental findings. These results highlight the robustness of the computational approach in identifying potential inhibitors and provide critical insights into the structure-activity relationships, aiding future drug development and therapeutic research.

This study describes the synthesis and biological evaluation of phenacyl-based sesamol derivatives as inhibitors of acetylcholinesterase (AChE), alpha-glycosidase (AG), and carbonic anhydrases I and II (CA I and II). The compounds were fully characterized by NMR and IR spectroscopy, and their inhibitory activities were assessed through enzyme assays and molecular docking. The derivatives showed potent inhibitory activity, with nano-molar K-i values ranging from 1.25 to 4.04 nM for AChE, 11.14 to 45.48 nM for AG, 54.63 to 103.89 nM for CA I, and 30.90 to 104.17 nM for CA II. Compound 9 displayed potent AChE (IC50 = 7.00 nM) and CA II (IC50 = 46.21 nM) inhibition, while compounds 10 was the most active against AG (IC50 = 25.67 nM), and compound 10 showed the highest activity against CA I (IC50 = 49.51 nM). Docking studies supported the experimental findings and clarified key binding interactions. These findings suggest that the synthesized derivatives may have potential as lead compounds for drug development, particularly in the treatment of enzyme-related disorders, and provide a foundation for further research in this area.

The aim of this study is to demonstrate the further synthetic capabilities of the reaction of N‑substituted phenylhydrazones with haloalkanes under modified catalytic olefination conditions. Studies of molecular geometry, electronic properties and intramolecular interactions of (Z)-N,N-dimethyl-2-(perfluorophenyl)-2-(2-phenylhydrazinylidene) acetamide (PFPA), which determine its stability, are presented. The structural and energy parameters, highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) energies, energy gap (∆E), molecular electrostatic potential (MEP), atomic charges, dipole moment, chemical reactivity descriptors, and NBO analysis were investigated using DFT at the B3LYP/6-31+G(d,p) level. The effects of hydrogen bonding on the geometry of molecule were observed. It was found the hydrazone and acetamide groups via the N30H37⋅⋅⋅N28 and N30H3⋅⋅⋅O31 hydrogen bonds form two pseudo-six-membered rings that look like a half chair. Molecular docking and dynamics studies of the title molecule to 5-HT1BR specific receptor were performed to understand the mechanism of its action nature. The received results indicate this acetamide behaves as a competitive inverse agonist of 5-HT1B subtype receptor. The pharmacophore model of PFPA for interaction with 5-HT1BR was proposed. Additionally, the effect of the compound on α-glycosidase enzyme was examined and IC50 and Ki values were calculated.

This study reports the synthesis of a novel ligand, sodium 6-(2,3-dicyanophenoxy)naphthalene-2-sulfonate (1), and the corresponding non-peripherally substituted metallophthalocyanines (MPcs) [M = Zn(II) (2), Ga(III) (3); X = Cl, In(III) (4); X = Cl]. These compounds were functionalized with 6-naphthoxy-2-sulfonic acid sodium salt groups. Given the limitations of conventional photodynamic therapy (PDT), we investigated the potential of sonophotodynamic therapy (SPDT), a dual-modality approach combining light and ultrasound, to enhance singlet oxygen (¹O2) production. Among the synthesized metallophthalocyanines, the zinc(II) complex (2) shows the highest ¹O2 production in both organic and aqueous media under both photochemical and sonophotochemical conditions, showing promise for SPDT applications. Furthermore, the inhibitory effects of these complexes on acetylcholinesterase (AChE) and human carbonic anhydrase isoenzymes (hCA I and II), important targets for Alzheimer’s disease, glaucoma, and epilepsy, were evaluated. The compounds showed strong inhibition with Ki values ranging from 130.31 ± 6.18 to 157.47 ± 9.37 µM for hCA I (compared to AZA: 177.41 ± 11.40 µM), 99.18 ± 8.13 to 106.72 ± 8.50 µM for hCA II (compared to AZA: 143.51 ± 9.94 µM) and 0.31 ± 0.03 to 1.21 ± 0.01 µM for AChE (compared to TAC: 1.24 ± 0.21 µM). Molecular docking revealed strong binding affinities: In(III)-Pc (4) showed the highest affinity for AChE (BE: -26.96 kcal/mol), while Ga(III)-Pc (3) preferentially bound to hCA I and II (BE: -13.90 and − 15.39 kcal/mol, respectively). These findings position the synthesized MPcs as multifunctional agents for SPDT and enzyme-targeted therapies.

Eminium rauwolffii (Blume) Schott var. rauwolffii is a member of the Araceae a large and mainly tropical family distributed worldwide. The Eminium species are utilized for various purposes including therapeutic uses in traditional medicine and as food. To analyze the antioxidant properties of water extract of E. rauwolffii (WEER) and ethanol extract of E. rauwolffii (EEER), 2,2’-azino-bis-3-ethylbenzthiazoline-6-sulphonic acid (ABTS•+) radical and 1,1-diphenyl-2-picrylhydrazyl (DPPH.) free radical scavenging, Fe3+-2,4,6-tris(2-pyridyl)-S-triazine (TPTZ) and Cu2+ reducing assays were studied. Antioxidant activities and reducing properties of both extracts were compared to standard antioxidants: BHT, BHA, α-Tocopherol, and Trolox. The IC50 values of EEER for radical scavenging were higher than those of standard antioxidants (25.35 ± 1.42 μg/mL for ABTS•+ and 106.80 ± 1.88 μg/mL for DPPH•). The total phenolic and flavonoid quantities in WEER and EEER were measured in the range of 189.78 ± 0.01 to 298.54 ± 0.01 mg GAE/g and 89.37 ± 0.01 to 178.95 ± 0.01 mg QE/g, respectively. The IC50 values for EEER and WEER against α-glycosidase, acetylcholinesterase (AChE), butyrylcholinesterase (BChE) and carbonic anhydrase I and II (hCA I and II) enzymes were 10.79 ± 5.61 to 13.18 ± 5.77, 36.14 ± 4.61 to 62.63 ± 1.67, 69.37 ± 7.36 to 37.48 ± 0.27, 81.30 ± 5.95 to 62.35 ± 8.03, and 29.34 ± 1.38 to 115.90 ± 3.3 µg/mL respectively. The antioxidant activity and enzymes inhibitory capacity of WEER were close, and comparable to the capacity demonstrated by the standards. The amount of sixteen compounds was identified from EEER. Numerous phytochemicals, including cynaroside, p-coumaric acid, cosmosiin, caffeic acid, and quinic acid, were quantitatively determined using the LC-MS/MS method. This clearly indicates that phenolic- and flavonoid-rich E. rauwolffii may have potential in the management of glaucoma, Alzheimer’s disease, diabetes, cardiovascular, and cancer disorders.