PubChem Research Articles

Isoliquiritigenin as a modulator of the Nrf2 signaling pathway: potential therapeutic implications.

Nuclear factor erythroid-2-related factor 2 (Nrf2), a transcription factor responsible for cytoprotection, plays a crucial role in regulating the expression of numerous antioxidant genes, thereby reducing reactive oxygen species (ROS) levels and safeguarding cells against oxidative stress. Extensive research has demonstrated the involvement of Nrf2 in various diseases, prompting the exploration of Nrf2 activation as a potential therapeutic approach for a variety of diseases. Consequently, there has been a surge of interest in investigating the Nrf2 signaling pathway and developing compounds that can modulate its activity. Isoliquiritigenin (ISL) (PubChem CID:638278) exhibits a diverse range of pharmacological activities, including antioxidant, anticancer, and anti-tumor properties. Notably, its robust antioxidant activity has garnered significant attention. Furthermore, ISL has been found to possess therapeutic effects on various diseases, such as diabetes, cardiovascular diseases, kidney diseases, and cancer, through the activation of the Nrf2 pathway. This review aims to evaluate the potential of ISL in modulating the Nrf2 signaling pathway and summarize the role of ISL in diverse diseases prevention and treatment through modulating the Nrf2 signaling pathway.

In-silico analysis of ethanol peel extract of Citrus sinensis on mercury chloride-induced prefrontal cortex damage in Wistar rat

This study evaluated the effect of ethanolic extract of Citrus sinensis peel on mercury chloride-induced changes in the prefrontal cortex of adult Wistar rats. Twenty-five Wistar rats were purchased and divided into five groups containing five animals in each group. Group 1 was administered with distilled water, Group 2, Group 3, Group 4, and Group 5 were administered with 5 mg/kg of mercury chloride only, 5 mg/kg of mercury chloride and 140 mg/kg Silymarin, 5 mg/kg mercury chloride and 1000 mg/kg of ethanoic extract of orange peel, and 5 mg/kg mercury chloride and 1500 mg/kg of ethanoic extract of orange peel. All administration was done orally and the administration lasted for 14 days. The animals were sacrificed humanely using 75 mg/kg ketamine intraperitoneally and prefrontal was dissected out. Part was homogenized in 0.1M phosphate buffered saline for the estimation of superoxide dismutase (SOD), and catalase (CAT) activities, and Malondialdehyde (MDA) level and the other part was fixed by immersion in 10 neutral buffered formal-saline for histological evaluation. The chemical structure of sixteen compounds from Citrus sinensis peel obtained from GC-MS analysis reported in the literature were retrieved from the PubChem compound database and the crystal structure of human peroxisome proliferator- activated receptor gamma (PPARγ; PDB:ID: 2P4Y) reported to increase the expression of catalase gene, human extracellular copper-zinc superoxide dismutase enzyme (PDB ID: 2JLP) and mammalian 15-lipoxygenase - 1 enzyme (PDB ID: 2P0M) responsible for the production of lipid peroxidation were retrieved from the PDB database. Ligands and protein preparation, docking and MM-GBSA relative binding free energy calculation were done in Maestro 2023.1. Data obtained was analyzed using the IBM SPSS (version 25) using one-way ANOVA and p-value < 0.05 was considered statistically significant. The results indicate that the MDA level in control Group(13.29±1.183 μmol) is statistically significantly lower compared to the Group 2 (21.88±1.96 μmol), group 3 (27.44±3.52 μmol), Group 4 (22.20±1.16 μmol) and Group 5 (25.40±3.13 μmol). No statistically significant difference was observed in SOD activity. The CAT activities in control group (53.51±6.83 nmol/ml) was statistically significantly lower compared to the group 2 (26.21±3.70 nmol/ml), Group 3 (27.17±5.32 nmol/ml), Group 4 (25.30±4.24 nmol/ml) and Group5 (26.59±4.22 nmol/ml).The present study suggests, ethanolic extract of Citrus sinensis peel have protective effects on mercury-induced changes in prelimbic part of the prefrontal cortex of adult Wistar rats.

Structure-based drug-development study against fibroblast growth factor receptor 2: molecular docking and Molecular dynamics simulation approaches

Developing new therapeutic strategies to target specific molecular pathways has become a primary focus in modern drug discovery science. Fibroblast growth factor receptor 2 (FGFR2) is a critical signaling protein involved in various cellular processes and implicated in numerous diseases, including cancer. Existing FGFR2 inhibitors face limitations like drug resistance and specificity issues. In this study, we present an integrated structure-based bioinformatics analysis to explore the potential of FGFR2 inhibitors-like compounds from the PubChem database with the Tanimoto threshold of 80%. We conducted a structure-based virtual screening approach on a dataset comprising 2336 compounds sourced from the PubChem database. Primarily, the selection of promising compounds was based on several criteria, such as drug-likeness, binding affinities, docking scores, and selectivity. Further, we conducted all-atom molecular dynamics (MD) simulations for 200 ns, followed by an essential dynamics analysis. Finally, a promising FGFR2 inhibitor with PubChem CID:507883 (1-[7-(1H-benzimidazol-2-yl)-4-fluoro-1H-indol-3-yl]-2-(4-benzoylpiperazin-1-yl)ethane-1,2-dione) was screened out from the study. This compound indicates a higher potential for inhibiting FGFR2 than the control inhibitor, Zoligratinib. The identified compound, CID:507883 shows >80% structural similarity with Zoligratinib. ADMET analysis showed promising pharmacokinetic potential of the screened compound. Overall, the findings indicate that the compound CID:507883 may have promising potential to serve as a lead candidate against FGFR2 and could be further exploited in therapeutic development.

Effects of Sesamin in Animal Models of Obesity-Associated Diseases: A Systematic Review and Meta-Analysis.

As living standards have improved and lifestyles have undergone changes, metabolic diseases associated with obesity have become increasingly prevalent. It is well established that sesamin (Ses) (PubChem CID: 72307), the primary lignans in sesame seeds and sesame oil, possess antioxidant and anti-inflammatory effects. In this study, a systematic review and meta-analysis of the effects of Ses on animal models of obesity-related diseases was performed to assess their impact on relevant disease parameters. Importantly, this study sought to provide insights for the design of future human clinical studies utilizing Ses as a nutritional supplement or drug. This study conducted a comprehensive search in PubMed, Web of Science, Embase, Scopus, and the Cochrane Library, identifying English language articles published from inception to April 2023. The search incorporated keywords such as "sesamin," "obesity," "non-alcoholic fatty liver disease," "type 2 diabetes mellitus," and "metabolic syndrome." The meta-analysis included 17 articles on non-alcoholic fatty liver disease, type 2 diabetes, and metabolic syndrome. Overall, the pooled results demonstrated that Ses significantly reduced levels of total serum cholesterol (P = .010), total serum triglycerides (P = .003), alanine transaminase (P = .003), and blood glucose (P < .001), and increased high-density lipoprotein cholesterol levels (P = .012) in animal models of nonalcoholic fatty liver disease. In the type 2 diabetes model, Ses mitigated drug-induced weight loss (P < .001), high-fat-diet-induced weight gain (P < .001), and blood glucose levels (P = .001). In the metabolic syndrome model, Ses was associated with a significant reduction in body weight (P < .001), total serum cholesterol (P < .001), total serum triglycerides (P < .001), blood glucose (P < .001), and alanine transaminase levels (P = .039). The meta-analysis results of this study suggest that Ses supplementation yields favorable effects in animal models of obesity-related diseases, including hypolipidemic, insulin-lowering, and hypoglycemic abilities, as well as organ protection from oxidative stress and reduced inflammation. PROSPERO registration No. CRD42023438502.

Discovery of the Inhibitor Targeting the SLC7A11/xCT Axis through In Silico and In Vitro Experiments.

In the development and progression of cervical cancer, oxidative stress plays an important role within the cells. Among them, Solute Carrier Family 7 Member 11 (SLC7A11/xCT) is crucial for maintaining the synthesis of glutathione and the antioxidant system in cervical cancer cells. In various tumor cells, studies have shown that SLC7A11 inhibits ferroptosis, a form of cell death, by mediating cystine uptake and maintaining glutathione synthesis. Additionally, SLC7A11 is also involved in promoting tumor metastasis and immune evasion. Therefore, inhibiting the SLC7A11/xCT axis has become a potential therapeutic strategy for cervical cancer. In this study, through structure-based high-throughput virtual screening, a compound targeting the SLC7A11/xCT axis named compound 1 (PubChem CID: 3492258) was discovered. In vitro experiments using HeLa cervical cancer cells as the experimental cell model showed that compound 1 could reduce intracellular glutathione levels, increase glutamate and reactive oxygen species (ROS) levels, disrupt the oxidative balance within HeLa cells, and induce cell death. Furthermore, molecular dynamics simulation results showed that compound 1 has a stronger binding affinity with SLC7A11 compared to the positive control erastin. Overall, all the results mentioned above indicate the potential of compound 1 in targeting the SLC7A11/xCT axis and treating cervical cancer both in vitro and in silico.

Functional characterization and structural prediction of hypothetical proteins in monkeypox virus and identification of potential inhibitors.

The excessive activation of the monkeypox virus (MPXV-Congo_8-156) is linked to various skin and respiratory disorders such as rashes, fluid-filled blisters, swollen lymph nodes and encephalitis (inflammation of the brain), highlighting MPXV-Congo_8-156 as a promising target for drug intervention. Despite the effectiveness of Cidofovir, in inhibiting MPXV activity, its limited ability to penetrate the skin and its strong side effects restrict its application. To address this challenge, we screened 500 compounds capable of penetrating the skin and gastrointestinal tract to identify potent MPXV inhibitors. Various characterization schemes and structural models of MPXV-Congo_8-156 were explored with bioinformatics tools like PROTPARAM, SOPMA, SWISS-MODEL and PROCHECK. Using molecular docking in PyRx, we evaluated the binding affinities of these compounds with MPXV-Congo_8-156 and identified the top five candidates ranging from - 9.2 to - 8.8kcal/mol. ADMET analysis indicated that all five compounds were safer alternatives, showing no AMES toxicity or carcinogenicity in toxicological assessments. Molecular dynamics (MD) simulations, conducted for 100ns each, confirmed the docking interactions of the top five compounds alongside the control (Cidofovir), validating their potential as MPXV inhibitors. The compounds with PubChem CID numbers 4061636, 4422538, 3583576, 4856107 and 4800629 demonstrated strong support in terms of root-mean-square deviation (RMSD), root-mean-square fluctuation (RMSF), radius of gyration (Rg), solvent-accessible surface area (SASA) value, hydrogen bond analysis, and Molecular Mechanics Poisson-Boltzmann Surface Area (MM-PBSA) analysis. Thus, our investigation identified these five compounds as promising inhibitors of MPXV, offering potential therapeutic avenues. However, further in vivo studies are necessary to validate our findings.

Copper metal-organic framework for selective detection of florfenicol based on fluorescence sensing in chicken meat

Using a hydrothermal technique, a highly sensitive metal-organic Cu-MOFs sensor has been created to detect florfenicol (FFC) fluorescent in chicken meat. The sensor has demonstrated the ability to respond to the presence of FFC in an aqueous solution with accuracy and selectivity, as evidenced by an increase in fluorescence intensity. The interactions and adsorption mechanism based on hydrogen bonding, π- π, and n-π interactions demonstrate the high sensitivity and specificity of Cu-MOFs towards. FFC was detected quantitatively with a recovery of 96.48–98.79% in chicken meat samples. Within a broad linear range of 1–50 μM, the Cu-MOFs nanosensor exhibits a fast response time of 1 min, a low limit of detection (LOD) of 2.93 μM, and a limit of quantification (LOQ) of 8.80 μM. The potential applicability of the Cu-MOFs nanosensor for the detection of FFC in food matrices is confirmed by the results obtained with high-performance liquid chromatography (HPLC). Chemical compoundsCopper (II) nitrate (PubChem CID: 18616); Terephthalic acid (PubChem CID: 7489); Polyvinyl pyrrolidone (PubChem CID: 486422059); N, N-dimethylformamide (PubChem CID: 6228); Ethyl alcohol (PubChem CID: 702); Hydrochloric acid (PubChem CID: 313); Sodium hydroxide (PubChem CID: 14798); Acetic acid (PubChem CID: 176); Trichloroacetic acid (PubChem CID: 6421); Florfenicol (PubChem CID: 114811).

Anticoronavirus activity of rhizome of Dryopteris crassirhizoma via multistage targeting of virus entry and viral proteases, Mpro and PLpro

Ethnopharmacological relevanceThe rhizome of Dryopteris crassirhizoma Nakai (Dryopteridaceae, RDC), a traditional East Asian herbal medicine, possesses a broad spectrum of medicinal properties, including anti-inflammatory, anticancer, antibacterial, and antiviral activities. Aim of the studyThis study investigates the 30% ethanolic extract of RDC's antiviral potential against human coronavirus OC43 (HCoV-OC43), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and its variants infections. Materials and methodsA 30% ethanolic extract of RDC or its components, filixic acid ABA (PubChem CID: 15081408) and dryocrassin ABBA (PubChem CID: 3082025) were treated with Human Coronavirus infection (HCoV-OC43, SARS-CoV-2 and its variants). The base peak chromatogram of RDC was evaluated using UPLC-Q/TOF Mass to identify the RDC, and the quantitative analysis of RDC compounds was performed using LC-MS/MS. A cytopathic effect (CPE) reduction assay, Western blot, immunofluorescence staining of viral protein expression, and qRT-PCR were performed to quantify the viral RNA copy numbers and determine the antiviral activity. The time-of-addition assay, the virus attachment, penetration, and virucidal assays, and SARS-CoV-2 Mpro and PLpro activity assay were used to elucidate the mode of action. ResultsRDC exhibited dose-dependent inhibition of HCoV-OC43–induced cytopathic effects, reducing viral RNA copy numbers and viral protein levels. Time-of-addition assays indicated that RDC targets the early stages of the HCoV-OC43 life cycle, inhibiting virion attachment and penetration with virucidal activity. Notably, filixic acid ABA and dryocrassin ABBA, constituents of RDC, reduced HCoV-OC43 viral RNA loads. Furthermore, RDC effectively blocked viral entry in pseudotyped lentivirus assays, involving spike proteins of SARS-CoV-2 Delta plus and South Africa variants, as well as control lentiviral particles expressing vesicular stomatitis virus glycoprotein G. Additionally, RDC demonstrated inhibition of SARS-CoV-2 infection and its variants by targeting viral proteases, namely main protease (Mpro) and papain-like protease (PLpro). ConclusionsThese findings underscore RDC's multistage approach to targeting viral infections by impeding virus entry and inhibiting viral protease activity. Therefore, RDC holds promise as a potent, broad-spectrum anticoronaviral therapeutic agent.

Transformation of cell wall pectin profile during postharvest ripening process alters drying behavior and regulates the sugar content of dried plums

This study evaluated the effects of postharvest ripening (0–6 days, D0–6) on cell wall pectin profile, infrared-assisted hot air-drying characteristics, and sugar content. Results showed that during postharvest ripening progress, the content of water-soluble pectin (WSP) and chelate-soluble pectin (CSP) increased while the content of Na2CO3-soluble pectin (NSP) and hemicellulose (HC) decreased. In addition, the average molecular weight of WSP increased while the average molecular weight of NSP decreased. Secondly, the drying time of plums with different postharvest ripening periods was in the order: D3 < D4 < D2 < D1 < D0 < D5 < D6. Furthermore, the sugar content of dried plums was mainly influenced by drying time, with three stages of sugar changes observed, tied to moisture content: (1) Sucrose hydrolyzes (50–85%); (2) Fructose and glucose degrade (15–50%); (3) Sorbitol degrades (15–42%). These findings indicate that the transformation of cell wall pectin profile during the postharvest ripening process alters drying behavior and regulates the sugar content of dried plums. Chemical compounds studied in this articleGalacturonic acid (PubChem CID: 439215); Acetone (PubChem CID: 180); Distilled water (PubChem CID: 962); Trans-1,2-Diaminocyclohexane-N, N, N, N′-tetraacetic acid (PubChem CID: 2723845); Na2CO3 (PubChem CID: 10340); Glucose (PubChem CID: 5793); fructose (PubChem CID: 2723872) sucrose (PubChem CID: 5988) sorbitol (PubChem CID: 5780) and Sodium borohydride (PubChem CID: 4311764).

Effect of osmanthus hydrolat on the aroma quality and volatile components of osmanthus black tea

Osmanthus fragrans is an evergreen shrub with a pleasant fragrance and a wide range of applications in many fields. The condensed hydrolat obtained during the drying process of its fresh flowers was collected in a low-temperature vacuum environment and its sensory evaluation and volatile components were studied. The main aroma compounds in Osmanthus fragrans were dihydro-β-ionone, nonanal, β-cyclocitral, β-ionone, benzaldehyde, α-ionone, and 6-methyl-5-hepten-2-one, whose contents were used as the main evaluation criteria, and the hydrolats obtained under different scenting and drying times were compared. This process can effectively collect the aroma components in Osmanthus fragrans and the optimal drying conditions were 50 °C for 5 h. The hydrolat was used to provide the scent of osmanthus black tea, which had a fresher and mellower taste, while the fragrance of osmanthus was abundant. These results show that osmanthus hydrolat can be used to provide the scent of floral black tea. Chemical compounds studied in this article(−)-Catechin (PubChem CID: 1203); (−)-epigallocatechin gallate (PubChem CID: 65064); (−)-epicatechin gallate (PubChem CID: 367141); (−)-epigallocatechin (PubChem CID: 72277); (−)-epicatechin (PubChem CID: 72276); (−)-gallocatechin gallate (PubChem CID: 199472); (−)-catechin gallate (PubChem CID: 6419835); (−)-gallocatechin (PubChem CID: 9882981).

Accumulation patterns of flavonoids and phenolic acids in different colored sweet potato flesh revealed based on untargeted metabolomics

Sweet potatoes are rich in flavonoids and phenolic acids, showing incomparable nutritional and health value. In this investigation, we comprehensively analyzed the secondary metabolite profiles in the flesh of different-colored sweet potato flesh. We determined the metabolomic profiles of white sweet potato flesh (BS), orange sweet potato flesh (CS), and purple sweet potato flesh (ZS) using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The CS vs. BS, ZS vs. BS, and ZS vs. CS comparisons identified a total of 4447 secondary metabolites, including 1540, 1949, and 1931 differentially accumulated metabolites. Among them, there were significant differences in flavonoids and phenolic acids. There were 20 flavonoids and 13 phenolic acids that were common differential metabolites among the three comparison groups. The accumulation of paeoniflorin-like and delphinidin-like compounds may be responsible for the purple coloration of sweet potato flesh. These findings provide new rationale and insights for the development of functional foods for sweet potatoes. List of compoundsKaempferol (PubChem CID: 5280863); Peonidin 3-(6”-p-coumarylglucoside) (PubChem CID: 44256849); Swerchirin (PubChem CID: 5281660); Trilobatin (PubChem CID: 6451798); 3-Geranyl-4-hydroxybenzoate (PubChem CID: 54730540); Eupatorin (PubChem CID: 97214); Icaritin (PubChem CID: 5318980); Isorhamnetin (PubChem CID: 5281654); Glucoliquiritin apioside (PubChem CID: 74819335); Brazilin (PubChem CID: 73384).

In-silico assessment of bioactive compounds from chewing stick (Salvadora persica) against N-acetylneuraminate lyase (5ZKA) of Fusobacterium nucleatum involved in salicyclic acid metabolism

BackgroundFusobacterium nucleatum is implicated in the formation of subgingival dental plaques. The main therapy of choice is the use of non-surgical periodontal therapy; however, this has been shown to be unable to remove Fusobacterium nucleatum completely informing the need for an alternative therapy. The aim of this study was to evaluate in-silico, the mechanism with which bioactive compounds from Chewing stick (Salvadora persica) mediate their action against F. nucleatum. MethodThe bioactive compounds 5-Hydroxymethylfurfural (PubChem CID: 237332), furan-2-carboxylic acid, 3-methyl-, trimethylsilyl ester (PubChem CID: 587050), and d-Erythro-Pentofuranose, 2-deoxy-1,3,5-tris-O-(trimethylsilyl) (PubChem CID: 525316) from S. persica and target protein N-acetylneuraminate lyase (5ZKA) were retrieved from literature and protein database, prepared and utilised for docking and molecular simulations using standard protocols with metronidazole and co-crystal as controls. In addition, the pharmacokinetic (ADMET) properties and density functional theory (DFT) were also evaluated ResultThe docking scores were -6.7 for the control co-crystal, -5.6 for metronidazole, -5.5 for 5-Hydroxymethylfurfural, -5.2 for d-Erythro-Pentofuranose, 2-deoxy-1,3,5-tris-O-(trimethylsilyl)- and -5.9 for furan-2-carboxylic acid, 3-methyl-, trimethylsilyl ester. Molecular simulation indicate RMSD and RMSF values suggestive of stable complexes during most of the simulation runs, especially so for 5-Hydroxymethylfurfural and Furan-2-carboxylic acid-3-methyl- trimethylsilyl ester that returned RMSD values less than 1.8 Å and RMSF values that were generally less than 2.0. Our ADMET prediction indicates that the test ligands had better pharmacokinetic than the standard drug except for furan-2-carboxylic acid and d-Erythro-Pentofuranose, 2-deoxy-1,3,5-tris-O- that showed hepatotoxicity. In addition, our DFT result indicated that the reactivity of the ligands were slightly less than that of metronidazole ConclusionThe ligands show promising drug-like potential that can be exploited further towards an alternative medication for managing F. nucleatum subgingival dental oral diseases.

Rational virtual screening, ADME, and molecular simulation studies of potential inhibitors of human superoxide dismutase 1 in a dysfunctional antioxidant system

Superoxide dismutase 1 (SOD1), a copper-dependent enzyme, facilitates the conversion of superoxide anions into hydrogen peroxide and oxygen, thereby regulating superoxide levels. Dysfunctions in SOD1 have been linked to neurodegenerative disorders such as amyotrophic lateral sclerosis, as well as liver and lung cancers. This study aimed to identify SOD1 modulators using in silico rational virtual enrichment screening, pharmacokinetics, docking, and molecular dynamic simulation (MDS). The findings yielded 38 compounds, predominantly exhibiting high gastrointestinal absorption but mostly non-permeable across the blood&amp;ndash;brain barrier, with few exhibiting inhibitory effects on selected cytochrome P450s. Molecular docking revealed that compound 1 (PubChem CID: 36791369) exhibited the highest binding affinity (&amp;minus;6.771 kcal&amp;middot;mol-1), followed by compound 19 (PubChem CID: 30935) with &amp;minus;6.468 kcal&amp;middot;mol-1, and compound 20 (PubChem CID: 135744521) with &amp;minus;5.978 kcal&amp;middot;mol-1. MDS and molecular mechanics/generalized Born surface area analysis indicated that the compound CID 36791369 &amp;ndash; SOD1 complex and compound CID 30935 &amp;ndash; SOD1 complex remained stable and energetically favorable under simulated physiological conditions at 0 ns and 100 ns. In conclusion, this study identified 38 compounds, among which compounds SN5, SN6, SN7, SN12, and SN25 emerged as potential inhibitors of SOD1 based on overall analyses. Further, research will be necessary to investigate the therapeutic effectiveness of these top five compounds in vitro and in vivo against SOD1.

Exploring the Antibacterial Potential of Artemisia judaica Compounds Targeting the Hydrolase/Antibiotic Protein in Klebsiella pneumoniae: In Vitro and In Silico Investigations.

Carbapenem antibiotic resistance is an emerging medical concern. Bacteria that possess the Klebsiella pneumoniae carbapenemase (KPC) protein, an enzyme that catalyzes the degradation of carbapenem antibiotics, have exhibited remarkable resistance to traditional and even modern therapeutic approaches. This study aimed to identify potential natural drug candidates sourced from the leaves of Artemisia judaica (A. judaica). The phytoconstituents present in A. judaica dried leaves were extracted using ethanol 80%. A reasonable amount of the extract was used to identify these phytochemicals via gas chromatography/mass spectrometry (GC/MS). One hundred twenty-two bioactive compounds from A. judaica were identified and subjected to docking analysis against the target bacterial protein. Four compounds (PubChem CID: 6917974, 159099, 628694, and 482788) were selected based on favorable docking scores (-9, -7.8, -7.7, and -7.5 kcal/mol). This computational investigation highlights the potential of these four compounds as promising antibacterial candidates against the specific KPC protein. Additionally, in vitro antibacterial assays using A. judaica extracts were conducted. The minimum inhibitory concentration (MIC) against the bacterium K. pneumonia was 125 μg/mL. Well-disk diffusion tests exhibited inhibition zones ranging from 10.3 ± 0.5 mm to 17 ± 0.5 mm at different concentrations, and time-kill kinetics at 12 h indicated effective inhibition of bacterial growth by A. judaica leaf extracts. Our findings have revealed the pharmaceutical potential of Artemisia judaica as a natural source for drug candidates against carbapenem-resistant pathogens.

Effects of polyols at low concentration on the release of sweet aroma compounds in model soda beverages

This study investigated the effect of polyols erythritol, d-mannitol, and maltitol on the volatility of aroma compounds γ-butyrolactone, 3-methyl-1-butanol, and 2-phenylethanol in aqueous solution. Headspace solid-phase microextraction/gas chromatography and diffusion-ordered nuclear magnetic resonance techniques were used to obtain information on aroma–food matrix interaction. Results demonstrated that adding polyols at final low concentrations of 5% or 10% (w/w) to an aqueous solution of 2-phenylethanol reduced the release of vapor-phase aromas, except in the case of 3-methyl-1-butanol, which was not affected by the presence of polyols in the liquid matrix. Polyols also reduced the diffusion coefficients of all three aroma compounds, probably due to friction between the molecules. At low polyol concentrations, aroma compound volatility and diffusion coefficient values were altered compared to those of aromas released from pure water. This observation is related to the physicochemical properties of the aroma compounds. These insights may help guide the use of the combination of aroma compounds and polyols in the formulation of sugar-free and reduced-sugar beverages. Chemical compoundsγ-butyrolactone (PubChem CID: 7302), 3-methyl-1-butanol (PubChem CID: 31260), 2-phenylethanol (PubChem CID: 6054), erythritol (PubChem CID: 222285), d-mannitol (PubChem CID: 6251), maltitol (PubChem CID: 493591).

Cheminformatics approach to identify andrographolide derivatives as dual inhibitors of methyltransferases (nsp14 and nsp16) of SARS-CoV-2

The Covid-19 pandemic outbreak has accelerated tremendous efforts to discover a therapeutic strategy that targets severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to control viral infection. Various viral proteins have been identified as potential drug targets, however, to date, no specific therapeutic cure is available against the SARS-CoV-2. To address this issue, the present work reports a systematic cheminformatic approach to identify the potent andrographolide derivatives that can target methyltransferases of SARS-CoV-2, i.e. nsp14 and nsp16 which are crucial for the replication of the virus and host immune evasion. A consensus of cheminformatics methodologies including virtual screening, molecular docking, ADMET profiling, molecular dynamics simulations, free-energy landscape analysis, molecular mechanics generalized born surface area (MM-GBSA), and density functional theory (DFT) was utilized. Our study reveals two new andrographolide derivatives (PubChem CID: 2734589 and 138968421) as natural bioactive molecules that can form stable complexes with both proteins via hydrophobic interactions, hydrogen bonds and electrostatic interactions. The toxicity analysis predicts class four toxicity for both compounds with LD50 value in the range of 500–700 mg/kg. MD simulation reveals the stable formation of the complex for both the compounds and their average trajectory values were found to be lower than the control inhibitor and protein alone. MMGBSA analysis corroborates the MD simulation result and showed the lowest energy for the compounds 2734589 and 138968421. The DFT and MEP analysis also predicts the better reactivity and stability of both the hit compounds. Overall, both andrographolide derivatives exhibit good potential as potent inhibitors for both nsp14 and nsp16 proteins, however, in-vitro and in vivo assessment would be required to prove their efficacy and safety in clinical settings. Moreover, the drug discovery strategy aiming at the dual target approach might serve as a useful model for inventing novel drug molecules for various other diseases.

NCoV-19 therapeutics using cucurbitacin I structural derivatives: an in silico approach

BackgroundCucurbitacins are present in some common vegetables as secondary metabolites and are used by the plants against harmful microbes. Exploration of this capability of natural product based substances against wide variety of microbes seems relevant due to the ease of availability of the resources and safety. In this regard, considering the current pandemic, the antiviral properties of these molecules with a subset of Cucurbitacin I structural derivatives have been screened. The inhibition potential of the phytochemicals was assessed by the stability of the protein–ligand complex formed with the nucleocapsid protein (PDB ID: 7CDZ) of SARS-CoV-2 by computational methods. The proposition of an alternate antiviral candidate that is cost-effective and efficient relative to existing formulations is the main objective of this work.ResultsServer-based molecular docking experiments revealed CBN19 (PubChem CID: 125125068) as a hit candidate among 101 test compounds, a reference molecule (K31), and 5 FDA-approved drugs in terms of binding affinities sorted out based on total energies. The molecular dynamics simulations (MDS) showed moderate stability of the protein-CBN19 complex as implied by various geometrical parameters RMSD, Rg, RMSF, SASA and hydrogen bond count. The ligand RMSD of 3.0 ± 0.5 Å, RMSF of Cα of protein with less than 5 Å, and smooth nature of SASA and Rg curves were calculated for the adduct. The binding free energy (− 47.19 ± 6.24 kcal/mol) extracted from the MDS trajectory using the MMGBSA method indicated spontaneity of the reaction between CBN19 and the protein. The multiple ADMET studies of the phytochemicals predicted some drug-like properties with minimal toxicity that mandate experimental verification. ConclusionsBased on all the preliminary in silico results, Cucurbitacin, CBN19 could be proposed as a potential inhibitor of nucleocapsid protein theoretically capable of curing the disease. The proposed molecule is recommended for further in vitro and in vivo trials in the quest to develop effective and alternate therapeutics from plant-based resources against COVID-19.

Development of chitosan-folate modified PLGA nanoparticles for targeted delivery of diosgenin as an anticancer agent

Diosgenin as a potential phytoconstituent and steroidal saponin manifested significant anticancer agents against various cancers. To enhance its solubility and bioavailability in cancer treatment, we loaded diosgenin (PubChem CID: 99474) in poly(lactic-co-glycolide) (PLGA) nanoparticle coated with folic acid-chitosan (Da-PFC-NPs). The diosgenin nano-formulation was characterized and its antioxidant and anticancer properties were surveyed respectively. The obtained results illustrated that the Da-PFC-NPs were spherical and stable with a size of 218 nm and a polydispersity index of 0.41. The Da-PFC-NPs indicated potential free radical scavenging using ABTS and DPPH assay. Meanwhile, it demonstrated selective toxicity against the TUBO breast cancer cell with IC50 values of 104.45 μg/ml and did not show toxicity on normal cells (I929 cell line). The invivo funding exhibited that Da-PFC-NPs notably altered the liver enzymes (AST, ALT, ALP) and immunoglobulins (IgA, IgG, IgM). Besides that, different doses of Da-PFC-NPs (50 and 100 mg/kg) remarkedly enhance the expression of caspase 3 and decrease HER2 genes. In light of this experiment, we can conclude that Da-PFC-NPs have promise as novel carrier for improving the delivery of diosgenin in cancer therapy.

In Silico Coformer Screening for Mefenamic Acid Cocrystallization

Cocrystallization is a widely used approach to enhance the solubility and dissolution characteristics of poorly soluble drugs. A pharmaceutical cocrystal is a multicomponent system composed of a solid active pharmaceutical ingredient (API) and a coformer, governed by non-covalent interactions. Screening for suitable coformers is essential to obtain an optimal cocrystal for specific drugs. This study aims to determine the drug-coformer interactions to select the most suitable coformer for cocrystal formation using the molecular docking method. Mefenamic acid, classified as a class II drug in the biopharmaceutical classification system (BCS), was used as the model drug. Two-dimensional structures of mefenamic acid (PubChem CID: 4044) and potential coformers were sourced from PubChem. Geometric optimization of all compounds was performed using GaussView 5.0.8 and Gaussian09 with the 3-21G basis set and Density Functional Theory (DFT) B3LYP method. The optimized compounds were prepared by adding hydrogen atoms and calculating Kollman partial charges using AutoDock 4.2. A grid box of size 40 Å × 40 Å × 40 Å was generated, with a maximum radius of 0.375 Å set as the surface distance in each simulation. A hundred conformations were run using the Lamarckian Genetic Algorithm. Interaction types and binding energies were analyzed using VMD 1.9.2 and BIOVIA Discovery Studio 2020 to compare interactions between mefenamic acid and each coformer. The results revealed that most coformer compounds formed interactions with mefenamic acid via hydrogen bonding and π–interactions. Saccharin demonstrated the most optimal interaction with mefenamic acid, with a binding free energy of –3.1 kcal/mol. Saccharin was identified as the most suitable coformer for mefenamic acid cocrystal formation based on the molecular docking study. Further experimental validation of saccharin is recommended to confirm its effectiveness in cocrystallization with mefenamic acid.

Facile superhydrophobic modification on HPMC film using polydimethylsiloxane and starch granule coatings

The excessive water sensitivity of hydroxypropyl methylcellulose (HPMC) films prevent them from being used extensively. In order to overcome this limitation, superhydrophobic HPMC films were meticulously crafted through the utilization of a composite of polydimethylsiloxane (PDMS) and ball-milled rice starch, corn starch, or potato starch (RS/CS/PS) for the coating process. Initially possessing hydrophilic properties, the HPMC Film (CA = 49.3 ± 1.8°) underwent a transformative hydrophobic conversion upon the application of PDMS, resulting in a static contact angle measuring up to 103.4 ± 2.0°. Notably, the synergistic combination of PDMS-coated HPMC with ball-milled starch demonstrated exceptional superhydrophobic attributes. Particularly, the treated HPMC-based film, specifically the HP-CS-2 h film, showcased an impressive contact angle of 170.5° alongside a minimal sliding angle of 5.2°. The impact of diverse starch types and the ball milling treatment on the PDMS/starch coatings and HPMC film was thoroughly examined using scanning electron microscopy (SEM), wide-angle X-ray diffraction (WAXS), and particle size analysis. These studies demonstrated that the low surface energy and roughness required for the creation of superhydrophobic HPMC-based films were imparted by the hierarchical structure formed by the application of PDMS/ball-milled starch. Chemical compounds studied in this articlePolydimethylsiloxane (PubChem CID: 24764); Hydroxypropyl methylcellulose (PubChem CID: 671); Ethyl acetate (PubChem CID: 8857).