Significant Inhibitory Activity Research Articles

The Trypsin Inhibitory Activity of Vigna unguiculata ssp. Sesquipedalis (Hawari Mae) Seeds Grown in Sri Lanka was Evaluated

Aims: This study aimed to screen the entire seed sample of Vigna unguiculata ssp sesquipedalis (Hawari mae) for serine protease inhibitory activity. Additionally, the study explored the impact of various factors such as temperature, pH, metal ions, detergent, oxidizing and reducing agents on the inhibitory activity. Methodology: A batch of Hawari Mae seeds was obtained from the Plant Genetic Resources Center in Sri Lanka. A concentration gradient of aqueous seed extracts was tested for Serine Inhibitory Activity (SIA). To carry out the SIA assay, seed extracts were mixed with trypsin in phosphoric acid buffer (pH 7.6) and casein was added as the substrate. The samples were then incubated at 37°C and trichloroacetic acid was used to stop the reaction. The supernatants were checked for absorbance at 280 nm and the percentage of serine inhibitory activity (SIA%) was calculated. All experiments were conducted three times to ensure accuracy. The inhibitory activities were tested under various conditions, including different temperatures, pH levels, metal ions, detergents, and oxidizing and reducing agents. Results: The crude extract containing 10% of the substance showed the highest level of trypsin inhibitory activity at 96.03±0.005%. This particular extract was selected for further analysis. The study revealed that the enzyme inhibition activity was highest at a temperature of 37°C (95.42±0.006%) and a pH of 7.6 (95.71±0.003%). It was observed that all tested metal ions, except Cu2+, significantly reduced (P<0.05) the trypsin inhibitory activity in Hawari mae. The presence of the detergent Triton X-100 did not significantly affect (P>0.05) the trypsin inhibitory activity of Hawari mae. However, the presence of DMSO and dithiothreitol significantly (P<0.05) reduced its activity. Conclusion: Significant trypsin inhibitory activity was observed in the seed extract of Hawari mae. Further studies on the effects of various physio-chemical parameters can aid in the purification and isolation of trypsin inhibitors.

Strontium and Copper Co-Doped Multifunctional Calcium Phosphates: Biomimetic and Antibacterial Materials for Bone Implants.

β-tricalcium phosphate (β-TCP) is a promising material in regenerative traumatology for the creation of bone implants. Previously, it was established that doping the structure with certain cations can reduce the growth of bacterial activity. Recently, much attention has been paid to co-doped β-TCP, that is explained by their ability, on the one hand, to reduce cytotoxicity for cells of the human organism, on the other hand, to achieve a successful antibacterial effect. Sr, Cu-co-doped solid solutions of the composition Ca9.5-xSrxCu(PO4)7 was obtained by the method of solid-phase reactions. The Rietveld method of structural refinement revealed the presence of Sr2+ ions in four crystal sites: M1, M2, M3, and M4. The M5 site is completely occupied by Cu2+. Isomorphic substitution of Ca2+ → (Sr2+and Cu2+) expands the concentration limits of the existence of the solid solution with the β-TCP structure. No additional phases were formed up to x = 4.5 in Ca9.5-xSrxCu(PO4)7. Biocompatibility tests were performed on cell lines of human bone marrow mesenchymal stromal cells (hMSC), human fibroblasts (MRC-5) and osteoblasts (U-2OS). It was demonstrated that cytotoxicity exhibited a concentration dependence, along with an increase in osteogenesis and cell proliferation. Ca9.5-xSrxCu(PO4)7 powders showed significant inhibitory activity against pathogenic strains Escherichia coli and Staphylococcus aureus. Piezoelectric properties of Ca9.5-xSrxCu(PO4)7 were investigated. Possible ways to achieve high piezoelectric response are discussed. The combination of bioactive properties of Ca9.5-xSrxCu(PO4)7 renders them multifunctional materials suitable for bone substitutes.

ANTAGONISTIC ACTIVITY OF WOOD-INHABITING XYLARIA SPECIES AGAINST OTHER FUNGI IN DUAL CULTURE EXPERIMENTS

In this survey, two wood‑inhabiting species – Xylaria polymorpha and Xylaria longipes (10 strains each) were evaluated in dual culture assay against 6 fungi: Aspergillus niger, Candida albicans, Fusarium solani, Mucor plumbeus, Penicillium polonicum, and Trichoderma viride. Detailed descriptions of the interspecific interactions, morphological changes and comparison of X. longipes and X polymorpha reaction types with each fungus are provided. The results indicate significant inhibitory activity of both X. longipes and X. polymorpha against A. niger, M. plumbeus, P. polonicum, F. solani, C. albicans with differences in reaction types on a strain specific level. Most commonly, co‑cultivating resulted in Xylaria species replacing fungi (60.8% of all interactions), with a partial replacement after initial deadlock with mycelial contact as the most frequent type of interaction. Inhibiting activity at a distance occurred in the majority of dual cultures of X. polymorpha with A. niger and P. polonicum (deadlock at a distance), and X. longipes with M. plumbeus (deadlock at a distance followed by a partial replacement). Among all tested cultures, T. viride turned out to be the only fungus suppressing Xylaria (except for X. polymorpha strains that formed a deadlock at mycelial contact). Based on the listed reaction types, for each studied Xylaria strain antagonism index was calculated, revealing that X polymorpha IBK 2720 had the highest value among all screened strains amounted to 20. The results indicate the effectiveness of Xylaria against tested fungi via contact antagonism and provide valuable insights for further investigations of novel biocontrol agents.

Discovery of new 2-(3-(naphthalen-2-yl)-4,5-dihydro-1H-pyrazol-1-yl)thiazole derivatives with potential analgesic and anti-inflammatory activities: In vitro, in vivo and in silico investigations

Joining the global demand for the discovery of potent NSAIDs with minimized ulcerogenic effect, new pyrazole clubbed thiazole derivatives 5a-o were designed and synthesized. The new derivatives were initially evaluated for their analgesic activity. Eight compounds 5a, 5c, 5d, 5e, 5f, 5h, 5m, and 5o showed higher activity than Indomethacin (potency = 105–130 % vs. 100 %). Subsequently, they were picked for further evaluation of their anti-inflammatory activity, ulcerogenic liability as well as toxicological studies. Derivatives 5h and 5m showed a potential % edema inhibition after 3 h (79.39 % and 72.12 %, respectively), with a promising safety profile and low ulcer indices (3.80 and 3.20, respectively). The two compounds 5h and 5m were subjected to in vitro COX-1 and COX-2 inhibition assay. The candidate 5h showed nearly equipotent COX-1 inhibition (IC50 = 38.76 nM) compared to the non-selective reference drug Indomethacin (IC50 = 35.72 nM). Compound 5m expressed significant inhibitory activities and a higher COX-2 selectivity index (IC50 = 87.74 nM, SI = 2.05) in comparison with Indomethacin (SI = 0.52), with less selectivity than Celecoxib (SI = 8.31). Simulation docking studies were carried out to gain insights into the binding interaction of compounds 5h and 5m in the vicinity of COX-1 and COX-2 enzymes that illustrated the importance of pyrazole clubbed thiazole core in hydrogen bonding interactions. The thiazole motif of compounds 5h and 5m exhibited a well orientation toward COX-1 Arg120 key residue by hydrogen bonding interactions. Compound 5h revealed an additional arene-cation interaction with Arg120 that could rationalize its superior COX-1 inhibitory activity. Compounds 5h and 5m overlaid the co-crystallized ligand Celecoxib I differently in the active site of COX-2. Compound 5m showed an enhanced accommodation with binding energy of − 6.13 vs. − 1.70 kcal/mol of compounds 5h. The naphthalene ring of compound 5m adopted the Celecoxib I benzene sulfonamide region that is stabilized by hydrogen-arene interactions with the hydrophobic sidechains of the key residues Ser339 and Phe504. Further, the core structure of compound 5m, pyrazole clubbed thiazole, revealed deeper hydrophobic interactions with Ala513, Leu517 and Val509 residues. Finally, a sensitive and accurate UPLC-MS/MS method was developed for the simultaneous estimation of some selected promising pyrazole derivatives in rat plasma. Accordingly, compounds 5h and 5m were suggested to be promising potent analgesic and anti-inflammatory agents with improved safety profiles and a novel COX isozyme modulation activity.

Discovery of novel acrylopimaric acid triazole derivatives as promising antifungal agents.

To further develop potential natural fungicides, two series of new acrylopimaric acid triazole derivatives were synthesized, and their antifungal activities were tested and evaluated. In vitro antifungal activity results indicated that compound 5m exhibited significant inhibitory activity against Rhizoctonia solani with an half maximal effective concentration (EC50) value of 1.528 mg/L. Its antifungal effect was comparable to that of the commercially available fungicide fluconazole, epoxiconazole and propiconazole (EC50 values of 1.441, 0.815 and 1.173 mg/L). Subsequently, in vivo studies were conducted on compound 5m, which revealed its significant protective and curative effects against R. solani. In addition, physiological and biochemical studies showed that compound 5m could disrupt the morphology and ultrastructure of R. solani mycelium, increase cell membrane permeability, inhibit ergosterol synthesis, and enhance the activity of defense enzymes in rice plants. Three-dimensional quantitative structure-activity relationship (3D-QSAR) studies revealed that the molecular structure significantly influenced the binding of compound 5m to the receptor, thereby enhancing its antifungal activity. Compound 5m exhibits excellent antifungal activity against R. solani, making it a promising candidate fungicide for the prevention and control of R. solani. © 2024 Society of Chemical Industry.

A Burkholderia cenocepacia-like environmental isolate strongly inhibits the plant fungal pathogen Zymoseptoria tritici.

The detrimental effects of fungal pathogens on crop yields are substantial. The overuse of chemical fungicides contributes not only to environmental pollution but also to the emergence of resistant pathogens. Investigating natural isolates with strong antagonistic effects against pathogens can improve our understanding of their ecology and develop new treatments for the future. We discovered and examined a unique bacterial strain that demonstrates significant inhibitory activity against several phytopathogens. Our research demonstrates that this strain has a wide spectrum of inhibitory actions against plant pathogens, functioning through a complex mechanism. This plays a vital role in the interactions between plant microbiota and phytopathogens.

An In Vitro Study on the Antibacterial Activity of Statins Against the Most Common Bacterial Pathogens Causing Respiratory Tract Infections in a Tertiary Care Hospital.

Introduction The vast pleiotropic effect of statins has intrigued many researchers to select them as potential candidates against bacterial infections. The role of statins against bacterial pathogens remains debatable. This study was undertaken to evaluate and compare the antibacterial effect of commonly available statins against the most frequently isolatedbacterial pathogens causing respiratory tract infections in our tertiary care hospital using sputum as a sample. Materials and methods The study was conducted in the Microbiology Laboratory of our hospital. Drugs including atorvastatin, rosuvastatin, and simvastatin were purchased in pure form from Sigma Aldrich. Dimethylsulfoxide (DMSO) was used as a solvent for all three drugs. The positive controls used were gentamycin and amoxicillin for Gram-negative and Gram-positive bacteria, respectively. Data regarding all the culture and sensitivity results of sputum samples of patients admitted to the Respiratory Intensive Care Unit over the past 12 months were analyzed. The most common bacterial pathogensStaphylococcus aureus, Klebsiella pneumoniae,and Streptococcus pneumoniae isolated from sputum specimens were taken for our study. The antibacterial effect of statins was studied using two methods: the agar cup diffusion method and the broth dilution method. The zone of inhibition and minimum inhibitory concentration of the drugs were calculated and analyzed. Statistical analysis was performed using GraphPad Prism software version 10.2.0. A one-way ANOVAtest was used to determine if there was any statistical difference between the different statins and antibiotic groups. An unpaired t-test was used to determine the statistical difference between the statins. Results and discussion For the agar cup diffusion method, our results displayed a lack of antibacterial activity of all three statinsatorvastatin, rosuvastatin, and simvastatin against all three bacterial strainsStaphylococcus aureus, Klebsiella pneumoniae,and Streptococcus pneumoniae after overnight incubation by agar cup method at concentrations of3.125 μg/ml, 6.25 μg/ml, 12.5 μg/ml, 25 μg/ml and 50 μg/ml, respectively. The zone of inhibition observed was less than 4 mm (resistant) for all the serial dilutions of atorvastatin, rosuvastatin, and simvastatin. For the broth dilution method, the ANOVA test showed amoxicillin and gentamicin to have high statistically significant microbial growth inhibitory activity (p-value< 0.005) compared to atorvastatin and rosuvastatin. Statistically, though atorvastatin showed significant antimicrobial activity compared to normal saline and rosuvastatin,thiswas not considered clinically significant as the antimicrobial activity shown by atorvastatin was very negligible compared to the controls used and did not correspondto the serial dilutions of the drug. Conclusion Atorvastatin, rosuvastatin, and simvastatin lacked antibacterial activity against all three bacterial strains isolated from sputum specimens:Staphylococcus aureus, Klebsiella pneumoniae, and Streptococcus pneumoniae.Hence, the use of statins as an antimicrobial drug for respiratory tract infections has limited applications.

Two new chemical constituents from the aerial parts of Tripterygium wilfordii

Tripterygium wilfordii has been historically employed as a conventional botanical insecticide and a plant of medicinal significance. A new dihydroagarofuran sesquiterpene (1) and a new acyclic compound (2), along with seven known compounds (3–9), have been isolated from the aerial parts of Tripterygium wilfordii. The identification of the structures of novel compounds were accomplished through comprehensive spectroscopic analyses, encompassing HRESIMS, NMR, UV, IR, and a comparative analysis with spectroscopic data from compounds previously characterised. In in-vitro bioassay, compound 8 exhibited significant inhibitory activity for NO release in LPS-induced RAW 264.7 cells, with an IC50 value of 15.7 μM.

Effect of P. corylifolia on the pharmacokinetic profile of tofacitinib and the underlying mechanism.

This work aimed to explore the mechanisms underlying the interaction of the active furanocoumarins in P. corylifolia on tofacitinib both in vivo and in vitro. The concentration of tofacitinib and its metabolite M8 was determined using UPLC-MS/MS. The peak area ratio of M8 to tofacitinib was calculated to compare the inhibitory ability of furanocoumarin contained in the traditional Chinese medicine P. corylifolia in rat liver microsomes (RLMs), human liver microsomes (HLMs) and recombinant human CYP3A4 (rCYP3A4). We found that bergapten and isopsoralen exhibited more significant inhibitory activity in RLMs than other furanocoumarins. Bergapten and isopsoralen were selected to investigate tofacitinib drug interactions in vitro and in vivo. Thirty rats were randomly allocated into 5 groups (n = 6): control (0.5% CMC-Na), low-dose bergapten (20mg/kg), high-dose bergapten (50mg/kg), low-dose isopsoralen (20mg/kg) and ketoconazole. 10mg/kg of tofacitinib was orally intervented to each rat and the concentration level of tofacitinib in the rats were determined by UPLC-MS/MS. More imporrantly, the results showed that bergapten and isopsoralen significantly inhibited the metabolism of tofacitinib metabolism. The AUC(0-t), AUC(0-∞), MRT(0-t), MRT(0-∞) and Cmax of tofacitinib increased in varying degrees compared with the control group (all p < 0.05), but CLz/F decreased in varying degrees (p < 0.05) in the different dose bergapten group and isopsoralen group. Bergapten, isopsoralen and tofacitinib exhibit similar binding capacities with CYP3A4 by AutoDock 4.2 software, confirming that they compete for tofacitinib metabolism. P. corylifolia may considerably impact the metabolism of tofacitinib, which can provide essential information for the accurate therapeutic application of tofacitinib.

Diterpenoid glucosides with anti-inflammatory activity from Sigesbeckia glabrescens

Six previously undescribed diterpenoid glucosides, along with four known compounds, were isolated from the aerial parts of Sigesbeckia glabrescens. The structures and absolute configurations of undescribed compounds were elucidated using extensive spectroscopic techniques, ECD calculations and chemical methods. Compounds 1 and 8 exhibited anti-inflammatory activity against LPS-induced NO production in RAW 264.7 macrophages, with compound 8 demonstrating significant inhibitory activity compared to positive control minocycline, boasting an IC50 value at 14.20 μM.

Amide alkaloids and neolignans from Piper hongkongense and their inhibitory activities of PCSK9 expression

Four undescribed amide alkaloids hongkongensines A-C and 1-(1-oxo-6-hydroxy-2E,4E-dodecadienyl)-piperidine, five known amide alkaloids, and three known neolignans were isolated from the aerial part of Piper hongkongense. The planar structures of these compounds were determined by detailed analyses of HR-ESI-MS and NMR data. The absolute configurations of hongkongensines A-C were elucidated by single-crystal X-ray diffraction analysis and ECD calculations. Moreover, the inhibitory activities of PCSK9 expression in vitro for all compounds were assessed by PCSK9 AlphaLISA screening. Kadsurenone (10) displayed a significant inhibitory activity at 5 μM with an inhibition rate of 51.98%, compared with 55.55% of berberine (BBR 5 μM).

Bridged NHC-Pd(II) complexes: Synthesis, DFT calculations, molecular docking, and investigation of catalytic and biological activities

Six palladium(II) (3a-f) complexes of the type [Pd2(μ-Cl)2(NHC)] were prepared by transmetallation of the corresponding Ag-NHC and [PdCl2(CH3CN)2] complexes, and their structures were successfully characterised by 1H NMR, 13C NMR, HRMS, FTIR and elemental analysis. Density functional theory (DFT) calculations were also realised for the complexes. The prepared complexes were assessed for their catalytic activity in the C-H arylation of 2-isobuthylthiazole as well as for their biological activities. As results, these complexes were found to be potent catalysts in the creation of C5-arylated 2-isobuthylthiazole derivatives via C-H bond activation reaction. Furthermore, biological activity analysis revealed that complex 3a exhibits high cytotoxicity towards both human colon carcinoma cell lines (HCT-116) and hepatocellular carcinoma cell lines (HepG-2) with IC50 values of 4.2 and 9.3 µMmL−1, respectively. Complex 3b also showed antioxidant activity comparable to that of BHT through DPPH and ABTS assays. Both complexes 3d and 3f also showed significant inhibitory activity towards the AChE enzyme with IC50 values of 5.06 and 2.52 µMmL−1, respectively. Finally, all complexes showed excellent antiparasitic activity, with 3b exhibiting strong antileishmanial activity against both L. major promastigotes and amastigotes. The interaction between the most cytotoxic complexes and DNA, envisaged as a potential mechanism of toxicity, was explored by means of docking studies. In summary, these prepared complexes have the potential to serve as potent catalysts for the synthesis of arylated 2-isobutylthiazole and biologically active agents, paving the way for numerous prospects in the fields of medicinal chemistry and organic synthesis.

Natural anti-neuroinflammatory inhibitors in vitro and in vivo from Aglaia odorata

Fifty compounds including seven undescribed (1, 13, 18–20, 30, 31) and forty-three known (2–12, 14–17, 21–29, 32–50) ones were isolated from the extract of the twigs and leaves of Aglaia odorata with anti-neuroinflammatory activities. Their structures were determined by a combination of spectral analysis and calculated spectra (ECD and NMR). Among them, compounds 13–25 were found to possess tertiary amide bonds, with compounds 16, 17, and 19–21 existing detectable cis/trans mixtures in 1H NMR spectrum measured in CDCl3. Specifically, the analysis of the cis–trans isomerization equilibrium of tertiary amides in compounds 19–24 was conducted using NMR spectroscopy and quantum chemical calculations. Bioactivity evaluation showed that the cyclopenta[b]benzofuran derivatives (2–6, 8, 10, 12) could inhibit nitric oxide production at the nanomolar concentration (IC50 values ranging from 2 to 100 nM) in lipopolysaccharide-induced BV-2 cells, which were 413–20670 times greater than that of the positive drug (minocycline, IC50 = 41.34 μM). The cyclopenta[bc]benzopyran derivatives (13–16), diterpenoids (30–35), lignan (40), and flavonoids (45, 47, 49, 50) also demonstrated significant inhibitory activities with IC50 values ranging from 1.74 to 38.44 μM. Furthermore, the in vivo anti-neuroinflammatory effect of rocaglaol (12) was evaluated via immunofluorescence, qRT-PCR, and western blot assays in the LPS-treated mice model. The results showed that rocaglaol (12) attenuated the activation of microglia and decreased the mRNA expression of iNOS, TNF-α, IL-1β, and IL-6 in the cortex and hippocampus of mice. The mechanistic study suggested that rocaglaol might inhibit the activation of the NF-κB signaling pathway to relieve the neuroinflammatory response.

Synthesis and In vitro Screening of Pyrazine-2-Carbohydrazide Derivatives as Potential Antimicrobial Agents

Herein, we report the design of a new set of pyrazine-2-carbohydrazide derivatives (T1–T20) and in silico investigations to evaluate their inhibition activity against the enzyme, decaprenylphosphoryl-[Formula: see text]-D-ribose 2′-epimerase (DprE1). The derivatives interact with the Cys387 residue of the enzyme’s active site through hydrogen bonds. Further, we synthesized these compounds and evaluated their efficacy against the M. tuberculosis H37Rv strain. Compounds T16 and T19 displayed promising antitubercular activity, boasting a minimal inhibitory concentration of 1.56 [Formula: see text]g/mL. Furthermore, we assessed the antibacterial activity of these compounds against a range of pathogens, including S. aureus, S. mutans, E. coli and [Formula: see text]Typhi. Additionally, we evaluated their antifungal potency against A. niger. Notably, compounds T4, T8, T9, T16 and T19 exhibited noteworthy antibacterial activity against tested bacterial strains. Compounds T4, T9, T16, T17, T18 and T19 showed significant inhibition activity against A. niger. Importantly, all active compounds demonstrated low cytotoxicity, with IC50 values exceeding 300 [Formula: see text]M, ensuring no harm to normal cells. To gain a deeper understanding of these compounds, we conducted in silico investigations to evaluate their pharmacokinetics and pharmacochemical properties. Additionally, we employed DFT studies to explore the electronic characteristics of these compounds, providing valuable insights into their potential applications in the pharmaceutical field.

Acremosides A-G, Sugar Alcohol-Conjugated Acyclic Sesquiterpenes from a Sponge-Derived Acremonium Species.

Seven new sugar alcohol-conjugated acyclic sesquiterpenes, acremosides A-G (1-7), were isolated from the cultures of the sponge-associated fungus Acremonium sp. IMB18-086 cultivated with heat-killed Pseudomonas aeruginosa. The structures were determined by comprehensive analyses of 1D and 2D NMR spectroscopic data. The relative configurations were established by J-based configuration analysis and acetonide derivatization. The absolute configurations were elucidated by the Mosher ester method and ECD calculations. The structures of acremosides E-G (5-7) featured the linear sesquiterpene skeleton with a tetrahydrofuran moiety attached to a sugar alcohol. Acremosides A (1) and C-E (3-5) showed significant inhibitory activities against hepatitis C virus (EC50 values of 4.8-8.8 μM) with no cytotoxicity (CC50 of >200 μM).

Phytochemical characterization and multifaceted bioactivity assessment of essential oil from Ptychotis verticillata Duby: Anti-diabetic, anti-tyrosinase, and anti-inflammatory activity

The aim of this study is to explore the pharmacological properties of the essential oil derived from Ptychotis verticillata Duby (PVEO), a medicinal plant native to Morocco, focusing on its antidiabetic, anti-tyrosinase, and anti-inflammatory effects. Additionally, the study aims to characterize the phytochemical composition of PVEO and evaluate its potential as a natural therapeutic alternative for various health conditions. To achieve this, phytochemical analysis was conducted using gas chromatography-mass spectrometry (GC-MS). Furthermore, in vitro assessments were conducted to investigate PVEO's antidiabetic activity by inhibiting α-amylase, xanthine oxidase, and α-glucosidase. Tests were also undertaken to evaluate the anti-inflammatory effect of PVEO on RAW 264.7 cells stimulated by lipopolysaccharide (LPS), as well as its efficacy as an anti-tyrosinase agent and its lipoxygenase inhibition activity. The results of the phytochemical analysis revealed that PVEO is rich in terpene compounds, with percentages of 40.35 % γ-terpinene, 22.40 % carvacrol, and 19.77 % β-cymene. Moreover, in vitro evaluations demonstrated that PVEO exhibits significant inhibitory activity against α-amylase, xanthine oxidase, and α-glucosidase, indicating promising antidiabetic, and anti-gout potential. Furthermore, PVEO showed significant anti-tyrosinase activity, with an IC50 of 27.39 ± 0.44 μg/mL, and remarkable lipoxygenase inhibition (87.33 ± 2.6 %), suggesting its candidacy for dermatoprotection. Additionally, PVEO displayed a dose-dependent capacity to attenuate the production of NO and PGE2, two inflammatory mediators implicated in various pathologies, without compromising cellular viability. The findings of this study provide a solid foundation for future research on natural therapies and the development of new drugs, highlighting the therapeutic potential of PVEO in the treatment of gout, diabetes, pigmentation disorders, and inflammation.

Design, Synthesis and Anticancer Activity of Substituted 1, 3-Thiazolidin-4-One Derivatives

Background: Cancer is the global cause of death worldwide. Anticancer drug development is the need in today’s scenario. Thiazolidine is the nucleus that shows several pharmacological activities like anticancer, anti-inflammatory, antioxidant, antibacterial, antifungal, antidiabetic, antihyperlipidemic, and antiarthritic activity. In the present work molecular docking Glide module (Schrodinger Inc., USA) has been used for ligand docking against the Polo-like kinase-1. The series of substituted 3-Benzothiazol-2-yl-2-phenyl)-thiazolidin-4-ones were synthesized by the microwave-assisted synthesis system (CEM, USA) and characterized by melting point, FT-IR, 1H NMR, 13C NMR, and HR-MS analysis. Results: Molecular docking studies shows good docking score as well as interactions. Among the synthesized compounds, BG2 had the highest docking score of -8.381, followed by BG8 (-8.19) and BG1 (-8.156). All the newly synthesized compounds were examined for their in vitro anticancer activity against breast cancer cell line MCF-7 by Sulforhodamine B (SRB) assay. Conclusion: BG1, BG2, BG3, BG4, BG5, BG8, BG9, BG10, BG11, BG12, and BG13 (GI50: &lt;80 µg/ml) exhibited significant cell growth inhibitory activity. These results indicate that compounds showing in-vitro activity by molecular docking studies and SRB assay could be lead compounds for further development of anticancer agents and suitable candidates for in-vivo anticancer activity.

Anti‐obesity potential of Polygonum minus Huds.: in vitro and in vivo evaluation

SummaryPolygonum minus (PM) has a rich traditional usage for health benefits, yet its potential as a natural‐based solution for obesity management remains unexplored. This study evaluated the antioxidant properties, inhibition of pancreatic lipase and α‐glucosidase activities, and metabolite profiles of PM aerial extracts harvested at 8, 10, and 12 weeks using 1H NMR‐based metabolomics. PM harvested at 12 weeks exhibited significant antioxidant and enzyme inhibition activities. NMR metabolomics unveiled nine major metabolites correlated to the bioactivities of 12‐week PM. LC–MS/MS profiling enabled the identification of flavonoids and phenolic acids, with the majority having sulfate, gallate, and glycoside moieties. Notably, in vivo experiments demonstrated that rats treated with 200 mg kg−1 and 400 mg kg−1 PM exhibited significantly lower (P &lt; 0.05) total body weight gain (39.03% and 52.59%, respectively) compared to negative control rats (69.95%), with the lower dose group also exhibiting reduced (P &lt; 0.05) fasting blood glucose levels. This study highlights the potential of 12‐week PM as a natural‐based solution in obesity management.

Anacardic acid derivatives with significant α-glucosidase inhibitory activity from Syzygium samarangense

Our continuous effort to search for antidiabetic constituents from the leaves of Syzygium samarangense resulted in the isolation of one new anacardic acid derivative, 2-[(Z)-nonadec-14-enyl]-6-hydroxylbenzoic acid (1) along with four known analogues (2−5). The new structure was elucidated by means of extensive spectroscopic data including 1D and 2D NMR along with HRESIMS. The anacardic acid derivatives were isolated from this species for the first time. All compounds exhibited significant inhibitory effect with IC50 value of 0.75−3.60 μM against α-glucosidase.

Coumarin linked to 2-phenylbenzimidazole derivatives as potent α-glucosidase inhibitors

α-Glucosidase inhibitors have emerged as crucial agents in the management of type 2 diabetes mellitus. In the present study, a new series of coumarin-linked 2-phenylbenzimidazole derivatives 5a–m was designed, synthesized, and evaluated as anti-α-glucosidase agents. Among these derivatives, compound 5k (IC50 = 10.8 µM) exhibited a significant inhibitory activity in comparison to the positive control acarbose (IC50 = 750.0 µM). Through kinetic analysis, it was revealed that compound 5k exhibited a competitive inhibition pattern against α-glucosidase. To gain insights into the interactions between the title compounds and α-glucosidase molecular docking was employed. The obtained results highlighted crucial interactions that contribute to the inhibitory activities of the compounds against α-glucosidase. These derivatives show immense potential as promising starting points for developing novel α-glucosidase inhibitors.