Significant Inhibitory Activity Research Articles

Anti- Inflammatory Activities Of The Methanol Leaf Extract And Fractions Of Elaesis Guineensis In In-Vivo Animals

Abstract Objective Objective of this paper is to investigate the preliminary anti-inflammatory property of the leaves and its fractions of Elaesis guineensis using egg induced albumin and formaldehyde induced arthritis models in rats. Method Egg albumin induced inflammation was induced by sub-plantar injection of 0.1 ml of fresh undiluted egg albumin. The volume of distilled water displaced by the treated paw was measured at 0.5,1, 2, 3, 4, 5, and 6 hours after induction of inflammation. Formaldehyde-induced arthritis was induced after 30 min by sub-plantar injection of 0.1 ml of 2.5% formaldehyde solution and was repeated on day 3. Arthritis was assessed by measuring the volume of distilled water displaced by the paw before induction of arthritis and once every day for ten days, starting from day one, after induction of arthritis. Results The acute toxicity test revealed that the plant extract was safe even at 5000 mg/kg dose level. The methanol extract (ME) showed a dose-dependent inhibition of egg albumin-induced acute inflammation that peaked at the dose of 200 mg/kg, while the fractions of the extract showed that the hexane and ethyl acetate fractions had the highest activity during the experiment. Similarly, the crude extract of the formaldehyde induced arthritis showed a dose-dependent inhibition making the 200 mg/kg the most active dose level. Additionally, it was observed that among the fractions of the extract the hexane fraction (HF) showed the most significant inhibitory activity when compared to other fractions Conclusion this study establishes that the methanol leaf extract and fractions ofElaesis guineensis possess significant anti-inflammatory activity

Synthesis and Antifungal Activity Evaluation of Novel L-Carvone-Based 1,3,4-Thiadiazole-amide Derivatives as a Potential Succinate Dehydrogenase Inhibitor.

In an effort to explore new-type high-efficiency antifungal agents, 25 novel L-carvone-based 1,3,4-thiadiazole-amide derivatives were designed, synthesized, and structurally characterized by IR, 1H NMR, 13C NMR, and high-resolution mass spectrometry (HRMS) analyses. The antifungal activity of the target compounds was preliminarily assayed at a concentration of 50 μg/mL, and boscalid, a commercialized fungicide identified as a succinate dehydrogenase inhibitor (SDHI), was employed as the positive control. It was found that all of the target compounds showed moderate to potent antifungal activity against the tested fungi compared to boscalid. Surprisingly, compound 4b exhibited broad-spectrum and significant inhibition activity against the growth of eight phytopathogenic strains with inhibitory rates of 67-89%. Further, the results of the EC50 value test suggested that the EC50 values of compound 4b against Physalospora piricola and Colletotrichum orbiculare were 16.33 and 18.06 μg/mL, respectively, and both of them were better than those of boscalid (16.64 and >50). Therefore, compound 4b deserves further study as a lead compound for novel fungicides. In addition, the inhibitory activity of compound 4b against succinate dehydrogenase (SDH) was evaluated as well to prove that compound 4b (IC50 = 3.38 μM) displayed higher SDH-inhibition activity than boscalid (IC50 = 7.02 μM). The binding mode of compound 4b and SDH was simulated by molecular docking and found to be similar to that of boscalid. The structure-activity relationships (SARs) of the target compounds were analyzed by establishing a 3D-QSAR model. Besides, a 4b-loaded complex 4b/CSTA on a reported L-carvone-based nanochitosan carrier CSTA containing the 1,3,4-thiadiazole-amide group was constructed, and its sustained release performance was investigated in the EtOH-H2O system (1:9, v/v). The complex 4b/CSTA exhibited preferred sustained release performance, indicating its potential for developing environmentally friendly nanofungicides.

Anti-Inflammatory Secoiridoids from the Medicinal Herb Gentianopsis barbata.

Five new secoiridoids, gentianopsins A-E (1-5), along with two known analogues (6 and 7) were isolated from the whole plants of the medicinal herb Gentianopsis barbata. Their structures were elucidated by a comparison of extensive spectroscopic analysis (1D and 2D NMR, and HRMS) and quantum chemical calculations. Gentianopsins A (1) and B (2) represented two unusual skeletons of trihomo-secoiridoids. Anti-inflammatory activity of these isolates was evaluated via suppressing the secretion of cytokines TNF-α and IL-6 in LPS-induced macrophages RAW264.7. Significant inhibitory activity was observed for compounds 3 and 7 on IL-6 secretion with IC50 values of 10.22 and 13.30 μM, respectively.

Gas Chromatography-Mass Spectrometry and Fourier Transform Infrared Spectroscopy Analysis of Potential α-Glucosidase Inhibitors from Terminalia catappa Leaf Extracts

Aims: Postprandial hyperglyceamia is often caused by insulin insufficiency or cellular glucose uptake complications, and conventional treatments often yield undesirable side effects. The aim of the current work was to assess the α-glucosidase inhibitory activities of T. catappa leaf extracts and use spectroscopic techniques to partially characterize possible inhibitors. Study Design: Phytochemical screening, enzyme inhibition assay and spectrometric and spectroscopic characterization of bioactive compounds from leaf extract and fractions of T. catappa. Place and Duration of Study: The entire work was carried out at the Department of Applied Chemistry and Biochemistry, University for Development Studies, Ghana within nine months. Methodology: T. catappa leaf extract and fractions were qualitatively screened for phytochemicals and their biological activity assessed in α-glucosidase inhibition assay. The potential enzyme inhibitors were characterized by Gas Chromatography-Mass Spectrometry (GC-MS) and Fourier Transform Infrared (FT-IR) Spectroscopy. Results: Phytochemical screening of the extract and the various solvent fractions revealed the presence of alkaloids, flavonoids, saponins, flavanol glycosides, phenolics, and terpenoids. The α-glucosidase inhibition potential of the crude leaf extract was concentration-dependent with a half-maximal inhibitory concentration (IC50) of 337.5 µg/ml. Solvent fractions from the crude extract demonstrated α-glucosidase inhibitory activity with IC50 values ranging from 170.40 µg/ml for ethyl acetate (EtOAc) fraction to 71.90 µg/ml for n-hexane (n-Hex) fraction. Acarbose, the control drug, demonstrated significant α-glucosidase inhibition activity in a similar pattern with IC50 of 6.16 µg/ml. The enzyme inhibition kinetics parameters, specifically the Michaelis constant (KM) and Maximum reaction velocity (Vmax) values, suggested that the inhibition of α-glucosidase by T. catappa extract followed a competitive mode. GC-MS and FT-IR analysis of the n-Hexane fraction identified the compounds Eugenol, Urs-12-en-24-oic acid, 3-oxo-, methyl ester (+)-, phytol, trans-isoeugenol, α-amyrin, and squalene as the potential antidiabetic agents that might be responsible for reducing postprandial blood glucose levels. Conclusion: These findings show that T. catappa leaf extract contains α-glucosidase inhibitors and therefore serves as a valuable resource in the discovery of natural anti-diabetic agents.

Phytochemical Content and Potential Antioxidants, Antimitotic, Antifungal Effects of Anabasis aretioïdes Coss. & Moq. (Chenopodiaceae)

Anabasis aretioides is an endemic species of the southwestern Algerian region. It is often used as a remedy for its medicinal, antioxidant, antidiabetic, anti-inflammatory, and antimicrobial effects.The aim of this work is to evaluate its biological activities by testing its antioxidant, antiproliferative (Allium cepa test), anti-inflammatory, and antifungal powers. Phytochemical screening of A. aretioides revealed the presence of tannins, free desquinones, terpenoids, fatty acids, saponins, C-heterosides, sterols, and triterpenoid. Furthermore, the in vitro evaluation of the aqueous and methanolic extracts of Anabasis aretioide leaves allowed us to observe the significant DPPH radical scavenging activity of the methanolic extract compared with that of vitamin C (the activity remains significant compared with that of the aqueous extract). The mitotic index (MI) of the methanolic extract revealed that a dose of 1 mg/100 mL had the greatest effect (MI=13.10%), followed by a dose of 2.5 mg/mL (MI=11.22%). In parallel, the analysis of the protective activity against protein denaturation of the extracts revealed that the methanolic extract was relatively superior and very important compared with diclofenac. Additionally, the methanolic extract of Anabasis aretioides against different fungal species revealed significant inhibitory activity against Aspergillus parasiticus, Penicillium glandicola, and Aspergillus at 100 mg/mL. Conclusion, Anabasis aretioides is a plant that may have interesting phytotherapeutic effects.

Cadophorin C, a new cyclic heptapeptide isolated from a mangrove-derived fungus Penicillium sp. GXIMD 03101

One new cyclic heptapeptide, cadophorin C (1), and one known analogue cadophorin B (2) were isolated from the mangrove-derived fungus Penicillium sp. GXIMD 03101 from the mangrove Acanthus ilicifolius L. The chemical structure of 1 was elucidated by comprehensive analysis of the spectroscopic data, including 1D and 2D NMR and HRESIMS, and the known compound was identified by comparing the data with literature values. Compounds 1 and 2 were screened for antibacterial activity and benign prostatic hyperplasia (BPH) inhibitory activity. The results showed that compounds 1 and 2 have weak activity against Vibrio harveyi with MIC values of 3.12 and 12.5 μg/mL, respectively. Compounds 1 and 2 have significant inhibitory activity against BPH with IC50 values of 2.62 and 2.23 μM, respectively.

Hydroxydiorygmone A, a New Guaiane-Sesquiterpene from the Cultured Lichen Mycobiont of Diorygma sp

Objective: Cultured mycobiont of the Vietnamese crustose-lichen Diorygma sp. has been chemically investigated. Biological activities including cytotoxicity against HepG2 cell line, α-glucosidase inhibition, and nitric oxide inhibitory activity were evaluated. Methods: Extensive spectroscopic methods (NMR and ECD) and HRESI mass data were employed for structural elucidation. These isolates were evaluated for their cytotoxicity against HepG2 cell line, α-glucosidase inhibition, and inhibitory activity toward nitric oxide production in LPS-stimulated RAW 264.7 cells. Results: Four compounds (1–4), including a new guaiane-sesquiterpene, hydroxydiorygmone A (1), along with three known analogues, diorygmones A and B (2 and 3) and pruinosone (4), were isolated and characterized. Compound 1 showed moderate α-glucosidase inhibition with an IC50 value of 160 ± 2.2 µM and significant inhibitory activity toward nitric oxide production in LPS-stimulated RAW 264.7 cells with an IC50 value of 8.11 ± 0.21 µM. Others were inactive in α-glucosidase inhibitory and nitric oxide inhibitory tests. Conclusion: A new guaiane-sesquiterpene, hydroxydiorygmone A (1) was isolated and showed moderate α-glucosidase inhibition with an IC50 value of 160 ± 2.2 µM and significant inhibitory activity toward nitric oxide production in LPS-stimulated RAW 264.7 cells with an IC50 value of 8.11 ± 0.21 µM.

In Vitro Cytotoxicity and Mechanistic Investigation of Quinazolin-4(1H)-One Linked Coumarin as a Potent Anticancer Agent.

Quinazolinone-coumarin conjugates synthesized through Late-Stage Functionalization approach are evaluated for their invitro biological activity for 60 human cancer cell lines representing nine different cancer types. Among the synthesized compounds, eight displayed significant growth inhibitory activity across a spectrum of cancer types, with compound 23 demonstrating particularly notable cytotoxicity. Further investigation involved a five-dose assay of compound 23 against NCI-60 cancer cell lines, revealing its efficacy at different concentrations. Additionally, binding studies elucidated its interaction with Human Serum Albumin (HSA) and DNA. The results indicated a strong binding affinity of 23 with HSA, evidenced by a high binding constant (2.26 × 105 M-1). Moreover, its interaction with DNA occurred via intercalation, specifically between the base pairs of DNA strands, with a binding constant of 5.51 × 104 M-1. This suggests that compound 23 has the ability to bind to both DNA and transport proteins, making it a promising pharmacophore with potential therapeutic applications.

Antibacterial activity of Ocimum sanctum L. Essential Oil against multidrug resistance Bacteria Vaginosis

The antibiotic resistance of Bacteria Vaginosis (BV) isolates intensifies vaginal morbidity and genital infections facilitating poor treatment outcome and severe vaginal pathology. The phytochemicals in Ocimum sanctum essential oil (OsEO) were investigated for their antibacterial activity against bacteria vaginosis and major metabolites on multidrug resistance (MDR) strains. Bacteria pathogens isolated from vaginal samples (n=40) obtained from patients with confirmed BV were analysed for hemolytic activity, biofilm production and profiled for antibiotic resistance. Extracted OsEO was profiled with GC-MS and analysed for antibacterial activity. Of the recovered bacteria pathogens (n=241) associated with vaginosis including Streptococcus pyogenes (34%), Staphylococcus aureus (31%) and Escherichia coli (10%) and less than 10% Klebsiella oxytoca, Enterobacter cloaca, Pseudomonas aeruginosa and Citrobacter freundii were identified. Significant rates of 21.6%, 4.6% and 2.3% were weak, mild and strong biofilm producers respectively and overall 26.6% were hemolytic strains (p<0.05). More than 60% resistance to ceftriaxone sulbactam, ampiclox, cefuroxime, cefotaxime, nalidixic acid and cefexime was observed in BV with significant proportion showing MARI>0.2 (p<0.05). Hierarchical clustering of MDR BV strains provided related clustered bacteria pathogens having a very low susceptibility to iminepem, cefuroxime, and amoxycillin/clavulanate. More than 1.2% saponin, alkaloids and flavonoids levels in OsEO gave significant inhibitory activities at IC50 (25.0μg/mL) and IC90 (50.0μg/mL) and significant inhibitory association with phytochemical compounds (eta=0.457, p=0.015). OsEO cyclohexene and methanoazulene metabolites showed significant antibacterial association with BV strains (p<0.05). The OsEO phytochemical metabolites showed antibacterial activity against multidrug resistance BV and identified cyclohexene and methanoazulene are promising candidates for developing formulations as topical antimicrobial agents for BV treatment.

Design, Synthesis and Biological Activity Evaluation of β-Carboline Derivatives Containing Nitrogen Heterocycles.

A series of β-carboline derivatives containing nitrogen heterocycles were designed and synthesized. All compounds were screened for their antitumor activity against four human tumor cell lines (A549, K562, PC-3, T47D). Notably, compound N-(4-(morpholinomethyl)phenyl)-2-((5-(1-(3,4,5-trimethoxyphenyl)-9H-pyrido[3,4-b]indol-3-yl)-1,3,4-oxadiazol-2-yl)thio)acetamide (8q) exhibited significant inhibitory activity against PC-3 cells with an IC50 value of 9.86 µM. Importantly, compound 8q effectively suppressed both the proliferation and migration of PC-3 cells. Mechanistic studies revealed that compound 8q induced cell apoptosis and caused the accumulation of reactive oxygen species (ROS), leading to cell cycle arrest in the G0/G1 phase in PC-3 cells.

Dipeptidyl Peptidase-4 Inhibitors: A Systematic Review of Structure-Activity Relationship Studies

Context: Dipeptidyl peptidase 4 (DPP-4) is a serine exopeptidase enzyme that hydrolyzes the amide bond at the N-terminal of peptides. This enzyme converts incretins, such as glucagon-like peptide I and glucose-dependent insulinotropic peptide, into their inactive forms, thereby preventing them from stimulating insulin secretion. Numerous studies have confirmed the role of DPP-4 in the pathophysiology of type 2 diabetes, leading to the development of various DPP-4 inhibitors. In recent years, research on DPP-4 inhibitors has expanded significantly, resulting in the creation of both non-peptidomimetic heterocyclic compounds and peptidomimetic scaffolds. Evidence Acquisition: This systematic review summarizes all recent advances related to DPP-4 inhibitors up to 2024. It begins by outlining the biochemical characteristics of DPP-4 and general pharmacological principles of DPP-4 inhibition, followed by an overview of the latest developments from recent publications. The review provides valuable insights into the pharmacophores necessary for ligand-protein interactions, aimed at understanding the structure-activity relationship of novel DPP-4 inhibitors. Data for this review was collected from sources including ScienceDirect, PubMed, and Scopus. Results: This review highlights various chemical scaffolds that have been explored in the development of novel DPP-4 inhibitors. It emphasizes scaffolds with significant DPP-4 inhibitory activity, including azoles, azines, sulfonamides, and quinolone motifs. The article also details the structure-activity relationships of newly developed analogs, providing a comprehensive overview of recent advancements in this area. Conclusions: Despite moderate progress in the development of novel DPP-4 inhibitors, emerging molecular aspects of DPP-4 intervention show great promise for future therapeutic developments.

Design, synthesis and antifungal activity of arylhydrazine analogs containing diphenyl ether fragments.

Succinate dehydrogenase (SDH) represents a critical target in the development of novel fungicides. To address the growing issue of resistance and safeguard the economic viability of agricultural production, the pursuit of new succinate dehydrogenase inhibitors (SDHIs) has emerged as a significant focus of contemporary research. In this project, 32 arylhydrazine derivatives containing diphenyl ether structural units were synthesized and evaluated for their fungicidal activities against Rhizoctonia solani, Sclerotinia sclerotiorum, Alternaria alternata, Gibberella zeae, Alternaria solani and Colletotrichum gloeosporioides. In an in vitro fungicidal activity assay, compound D6 showed significant inhibitory activity against R. solani with a half-maximum effective concentration (EC50) of 0.09 mg L-1. The in vivo fungicidal activity demonstrated that compound D6 inhibited R. solani by 95.39% in rice leaves, which was significantly better than that of boscalid (85.76%). The results of SDH enzyme assay, molecular docking simulation, mitochondrial membrane potential assay, cytoplasmic release studies and morphological observations demonstrated that the target compound D6 not only had significant SDH inhibitory activity, but also affected the membrane integrity of mycelium. Bioactivity screening and validation of the mechanism of action indicated that compound D6 was a potentially unique SDHI, acting on SDH while also affecting cell membrane permeability, which deserved further study. © 2024 Society of Chemical Industry.

In Silico and ADMET Studies of Spiro-Quinazoline Compounds as Acetylcholine Esterase Inhibitors Against Alzheimer's Disease.

Alzheimer's disease (AD) is a prevalent neurodegenerative condition characterized by progressive cognitive decline and memory impairment resulting from the degeneration and death of brain neurons. Acetylcholinesterase (AChE) inhibitors are used in primary pharmacotherapy for numerous neurodegenerative conditions, providing their capacity to modulate acetylcholine levels crucial for cognitive function. Recently, quinazoline derivatives have emerged as a compelling model for neurodegenerative disease treatment, showcasing promising pharmacological features. Their unique structural features and pharmacokinetic profiles have sparked interest in their potential efficacy and safety across diverse neurodegenerative disorders. The exposure of quinazoline derivatives as a potential therapeutic way underscores the imperative for continued research exploration. Their multifaceted mechanisms of action and ability to target various pathways implicated in neurodegeneration offer exciting prospects for developing novel, effective, and well-tolerated treatments. Further investigations into their pharmacological activities and precise therapeutic roles are essential to advance our understanding of neurodegenerative disease pathophysiology and promote the development of modern therapeutic strategies to address this critical medical challenge. Quinazoline derivatives have gained eminent acetylcholinesterase (AChE) inhibitory activity. Their ability to effectively modulate AChE activity makes them promising candidates for treating neurological disorders, particularly Alzheimer's disease (AD). Their intricate molecular structures confer selectivity and affinity for AChE, offering potential for the development of novel therapeutic agents targeting cholinergic pathways. Hence, in this study, we designed, synthesized, and characterized a series of spiro[cycloalakane-1,2'-quinazoline derivatives (1-6) to assess their possible AChE inhibiting ability using docking into the active sites. The AChE inhibitory potential of spiro[cycloalkane-1,2'-quinazoline derivatives (1-6) was explored via docking studies of the AChE active site. The findings revealed significant inhibitory activity and highlighted the promising nature of these derivatives. The synthesized spiro[cycloalkane-1,2'-quinazoline derivatives (1-6) exhibited their notable potential as AChE inhibitors. The observed significant inhibitory activity suggested that these derivatives warrant further exploration as candidates for developing therapeutic agents in AChE inhibitory pathways. This study emphasizes the relevance of quinazoline derivatives in searching for novel treatments for neurological disorders, particularly associated with cholinergic dysfunction, and they could be a useful alternative therapeutic agent.

Physivitrins I–R, lanostane triterpenoids with anti-inflammatory activities from the fungus Physisporinus vitreus

Chemical investigation on the rice fermentation of the fungus Physisporinus vitreus led to the isolation of ten previously undescribed lanostane triterpenoids, physivitrins I–R, and three known analogues. The new structures were elucidated on the basis of extensive spectroscopic methods, including 1D & 2D NMR, HRESIMS, UV and ECD. Physivitrins I and P exhibited significant inhibitory activities against NO production in LPS-activated RAW267.4 macrophages with IC50 values of 8.2 and 11.5 μM, respectively. The comprehensive data indicated that P. vitreus is rich in lanostane triterpenes and has potential anti-inflammatory application prospects.

Design, synthesis, and biological evaluation of 2,4-dimorpholinopyrimidine-5-carbonitrile derivatives as orally bioavailable PI3K inhibitors.

Phosphoinositide-3-kinase (PI3K) is overexpressed in many tumors and is, thus, an ideal target for cancer treatments. Accordingly, there is an urgent need for the development of PI3K inhibitors with high potency and low toxicity. In this study, we designed and synthesized a series of 2,4-dimorpholinopyrimidine-5-carbonitrile derivatives, which were evaluated for their PI3K inhibitory potency. Compound 17p demonstrated comparable PI3Kα inhibitory activity (IC50: 31.8 ± 4.1nM) to the positive control, BKM-120 (IC50: 44.6 ± 3.6nM). In addition, 17p showed significant inhibitory activity against PI3Kδ (IC50: 15.4 ± 1.9nM) and significant isoform selectivity against PI3Kβ, PI3Kγ, and mTOR. Furthermore, 17p exhibited good antiproliferative activities against cancer cell activity and good safety in the Ames and hERG tests while having outstanding liver microsomal stability in vitro, with half-lives of 38.5min in rats and 127.9min in humans. In addition, in an apoptosis assay, 17p could induce dose-dependent cytotoxicity in the ovarian cancer cell line A2780. In a pharmacokinetic study, 17p was stable (T ½: 2.03h) and showed high bioavailability (46.2%). Collectively, these results indicate that 17p could be a promising PI3K agent for cancer treatment.

Some novel synthesis 2-aroyl-1-acetylhydrazine derivatives: An assessment of their biological activity as therapeutic agents

Our study provides valuable insights into the anti-cancer activity of novel acetyl hydrazine derivatives as TOP2B inhibitors in breast cancer cells. Molecular docking studies were performed to evaluate the putative bonding mode of the synthesized compounds (3a, 4, 5a,b, and 6a,b). The obtained compounds were characterized using 1H NMR and 13C NMR. Most of the compounds exhibited significant inhibitory activity against breast cancer cell lines. Among them, compound (6b) demonstrated a remarkable anti-cancer effect by inducing G2/M phase cell cycle arrest and apoptosis.

Penijanacoranes A—F, Acorane‐Type Sesquiterpenes from a Deep Sea‐Derived Fungus Penicillium janthinellumSH0301

Comprehensive SummarySix new acorane‐type sesquiterpenes, named penijanacoranes A—F (1—6), as well as one known eudesmane sesquiterpenoid 1α,6β,11‐eudesm‐triol (7) have been isolated from a deep‐sea‐derived fungus Penicillium janthinellum SH0301. Their structures and absolute configurations were established by the comprehensive spectroscopic analysis, TDDFT‐ECD calculations, and X‐ray diffraction. Penijanacorane A (1) was identified as a rare acorane‐type sesquiterpene lactone featuring a novel 6/5/6 tricyclic system, while penijanacoranes E and F (5 and 6) represented undescribed examples of nor‐acorane sesquiterpenes at C‐1. Penijanacorane C (3) exhibited significant inhibitory activity against LPS‐induced NO production in Raw264.7 macrophages with an IC50 value of 6.23 μM, which was more potent than that of positive control dexamethasone (IC50 = 11.49 μM). This study expanded the chemical diversity of acorane‐type sesquiterpenoids and revealed that compound 3 was a potential molecule for anti‐inflammatory agents.

Computational identification of Vernonia cinerea-derived phytochemicals as potential inhibitors of nonstructural protein 1 (NSP1) in dengue virus serotype-2.

Dengue virus (DENV) infection, spread by Aedes aegypti mosquitoes, is a significant public health concern in tropical and subtropical regions. Among the four distinct serotypes of DENV (DENV-1 to DENV-4), DENV-2 is associated with the highest number of fatalities worldwide. However, there is no specific treatment available for dengue patients caused by DENV-2. This study aimed to identify inhibitory phytocompounds in silico in Vernonia cinerea (V. cinerea), a widely used traditional medicinal plant, for treating DENV-2 associated illnesses. The chemical structures of 17 compounds from V. cinerea were sourced from the Indian Medicinal Plants, Phytochemistry, and Therapeutics (IMPPAT) database. These compounds underwent geometry optimization, were screened against nonstructural protein 1 (NSP1) of DENV-2, and further validated through molecular dynamics simulations (MDS). Baicalein, an established drug against DENV-2, was used for validation in molecular screening, MDS, and MM-GBSA analyses. Among these compounds, Beta-amyrin, Beta-amyrin acetate, Chrysoeriol, Isoorientin, and Luteolin showed promising potential as inhibitors of the NSP1 of DENV-2, supported by the results of thermodynamic properties, molecular orbitals, electrostatic potentials, spectral data and molecular screening. Besides, these compounds adhered to the Lipinski's "rule of 5", showing no hepatotoxicity/cytotoxicity, with mixed mutagenicity, immunotoxicity, and carcinogenicity. Furthermore, final validation through MDS confirmed their potential, demonstrating stable tendencies with significant inhibitory activities against NSP1 of DENV-2 over the control drug Baicalein. Among the screened compounds, Chrysoeriol emerged as the most promising inhibitor of NSP1 of DENV-2, followed by Luteolin and Isoorientin. Taken together, our results suggest that Chrysoeriol is the best inhibitor of NSP1 of DENV-2, which could be evaluated as a therapeutic agent or a lead compound to treat and manage DENV-2 infections.

In vitro Anti-oxidant, Alpha-Amylase, and Alpha-Glucosidase Inhibition Studies of Physica aipolia (Ehrh.ex Humb.) Furnr

Background: Diabetes prevalence is progressively rising everywhere, particularly in developing countries. Lichens have evolved into a rich source of innovative bioactive chemicals with their anti-oxidant capabilities, widening the scope of well-documented and effective diabetes treatment. Objective: The main objectives of this study were to perform in vitro alpha-amylase, alphaglucosidase inhibition analysis, and anti-oxidant of lichen Physica aipolia. Method: Folin Ciocalteu’s reagent was used to determine the total phenolic content for biological activities. The Aluminum trichloride method was used to determine total flavonoid content, and the free radical assay method was used to determine the antioxidant activity of P. aipolia using 2,2- diphenyl-1-picrylhydrazyl (DPPH). Moreover, substrate 2-Chloro-4-nitrophenyl-α-D-maltotrioside (CNPG3) and substrate-nitrophenyl-α-D-glucopyranose (p-NPG) were used for the determination of alpha-amylase and alpha-glucosidase inhibition activities respectively, and molecular docking was performed by Auto Dock Vina. Results: Total phenolic and flavonoid contents present in P. aipolia were 37.41 ± 2.87 mg GAE/g and 5.53 ± 0.95 mg QE/g, respectively. For anti-oxidant inhibition activity, crude extract of methanol showed an IC50 value of 15.324 ± 0.80 μg/mL. Furthermore, a methanolic crude extract showed significant inhibition activities against alpha-amylase (IC50 = 178.50 ± 1.10 μg/mL) and alphaglucosidase (IC50 = 76.10 ± 0.91 μg/mL). During in silico analysis, zeorin showed an effective binding affinity with -7.9 kcal/mol, and Atranorin showed -7.4 kcal/mol in the orthosteric site of the protein. Conclusion: Physica aipolia exhibits the potential to impact biological functions, demonstrating antidiabetic properties, as confirmed by molecular docking analysis in silico.

Fabrication of two novel two-dimensional copper-based coordination polymers regulated by the “V”-shaped second auxiliary ligands as high-efficiency urease inhibitors

Two novel copper-based coordination polymers (Cu-CPs) had been presented based on mixed ligands. The synthetic Cu-CP-1 and Cu-CP-2 were derived from a combination of two distinct forms of “V”-shaped bis-pyridine-bis-amide ligands and 1,2,4-benzenetricarboxylic acid (1,2,4-H3BTC). Distinct grid windows were seen in the simplified two-dimensional (2D) layers of the Cu-CPs due to the variable length of ligand regulation. These Cu-CPs had the potential to act as urease inhibitors (UIs), and the mechanisms responsible for their inhibition were extensively studied. The results indicated that both Cu-CPs exhibited significant urease inhibitory activities with urease inhibition rates of 88.02 % and 88.87 % at 100 µM and semi-inhibitory levels of IC50 of 0.92 ± 0.05 µM and 0.87 ± 0.03 µM, respectively. Furthermore, the inhibitory activities of the Cu-CPs were higher than those of the standard thiourea. An investigation of the enzyme kinetics of the Cu-CPs using Lineweaver–Burk (L–B) plots at various inhibitor doses demonstrated their non-competitive inhibitory nature, enhancing our comprehension of the possible mechanism by which these Cu-CPs exert urease inhibition. Furthermore, molecular docking was used to verify the interactions between Cu-CPs and the urease active site. The findings of the urease inhibition studies were good, and the impact of Cu-CP complexes on urease inhibition was examined using density functional theory (DFT) simulations.