Good Inhibitory Activity Research Articles

New 1,2,3-triazole/1,2,4-triazole hybrids linked to oxime moiety as nitric oxide donor selective COX-2, aromatase, B-RAFV600E and EGFR inhibitors celecoxib analogs: design, synthesis, anti-inflammatory/anti-proliferative activities, apoptosis and molecular modeling study

A new series of bis-triazole 19a-l was synthesised for the purpose of being hybrid molecules with both anti-inflammatory and anti-cancer activities and assessed for cell cycle arrest, NO release. Compounds 19c, 19f, 19h, 19 l exhibited COX-2 selectivity indexes in the range of 18.48 to 49.38 compared to celecoxib S.I. = 21.10), inhibit MCF-7 with IC50 = 9–16 μM compared to tamoxifen (IC50 = 27.9 μM). and showed good inhibitory activity against HEP-3B with IC50 = 4.5–14 μM compared to sorafenib (IC50 = 3.5 μM) (HEP-3B). Moreover, derivatives 19e, 19j, 19k, 19 l inhibit HCT-116 with IC50 = 5.3–13.7 μM compared to 5-FU with IC50 = 4.8 μM (HCT-116). Compounds 19c, 19f, 19h, 19 l showed excellent inhibitory activity against A549 with IC50 = 3–4.5 μM compared to 5-FU with IC50 = 6 μM (A549). Compounds 19c, 19f, 19h, 19 l inhibit aromatase (IC50 of 22.40, 23.20, 22.70, 30.30 μM), EGFR (IC50 of 0.112, 0.205, 0.169 and 0.066 μM) and B-RAFV600E (IC50 of 0.09, 0.06, 0.07 and 0.05 μM).

Synthesis of nitro‐containing isoquinoline‐1,3‐diones with tert‐butyl nitrite

AbstractAn efficient synthetic method for the nitro‐containing isoquinoline‐1,3‐diones has been achieved with tert‐butyl nitrite. This reaction features metal‐free, safety, simple operation and mild reaction conditions, which represents the first example of using stable and safe tert‐butyl nitrite as the nitro precursor for the synthesis of nitro‐containing isoquinoline‐1,3‐diones. Furthermore, both the control experiments and density functional theory calculations (DFT) have confirmed that the reaction was occurred through the radical reactions. In addition, the representative compounds 3a and 3i displayed potential good inhibitory activities for the plant height of rape and the compound 3a displayed potential promotion activity of the root length for barnyard grass.

Active peptides with hypoglycemic effect obtained from hemp (Cannabis sativa L) protein through identification, molecular docking, and virtual screening.

Hemp (Cannabis sativa L) seeds are rich in proteins of high nutritional value, which makes the study of beneficial properties of hemp seed proteins and peptides, such as hypotensive and hypoglycemic effects, increasingly attractive. The present results confirm the good processability and stability of the hemp protein hydrolysate obtained by enzymatic hydrolysis of non-dehulled hemp seed meal (NDHM). Six peptides with potential hypoglycemic activity were obtained by ethanol-graded precipitation, Nano LC-Q-Orbitrap-MS/MS mass spectrometry, and computerized virtual screening. Further, validation experiments for in vitro synthesis showed that TGLGR, SPVI, FY, and FR exhibited good α-glucosidase inhibitory activity, respectively. Animal experiments showed that the hemp protein peptides modulated blood glucose and blood lipids in hyperglycemic rats. These results indicate that hemp protein peptides can reduce blood glucose levels in hyperglycemic rats, suggesting that hemp proteins may be a promising natural source for the prevention and treatment of hyperglycemia.

A Novel Bifunctional μOR Agonist and σ1R Antagonist with Potent Analgesic Responses and Reduced Adverse Effects.

Bifunctional ligands possessing both μOR agonism and σ1R antagonism have shown promise in producing strong analgesic effects with reduced opioid-related side effects. However, the μOR agonism activity of most dual ligands diminishes compared with classical opioids, raising concern about their effectiveness in managing nociceptive pain. In this study, a new class of dual μOR agonist/σ1R antagonist was reported. Through structure-activity relationship analyses, we identified the optimal compound, 4x, which displayed picomolar μOR agonism activity (EC50: 0.6 ± 0.2 nM) and good σ1R inhibitory activity (Ki: 363.7 ± 5.6 nM) with excellent selectivity. Compound 4x exhibited robust analgesic effects in various pain models, with significantly reduced side effects. Importantly, compound 4x also possessed good safety profiles and no abnormalities were observed in biological parameters even under a high dosage. Our findings suggest that 4x may be a promising lead compound for developing safer opioids and warrants further in-depth studies.

Discovery of a Dual Tubulin and Neuropilin-1 (NRP1) Inhibitor with Potent In Vivo Anti-Tumor Activity via Pharmacophore-based Docking Screening, Structure Optimization, and Biological Evaluation.

Dual inhibition of tubulin and neuropilin-1 (NRP1) may become an effective method for cancer treatment by simultaneously killing tumor cells and inhibiting tumor angiogenesis. Herein, we identified dual tubulin/NRP1-targeting inhibitor TN-2, which exhibited good inhibitory activity against both tubulin polymerization (IC50 = 0.71 ± 0.03 μM) and NRP1 (IC50 = 0.85 ± 0.04 μM). Importantly, it significantly inhibited the viability of several human prostate tumor cell lines. Further mechanism studies indicated that TN-2 could inhibit tubulin polymerization and cause G2/M arrest, thereby inducing cell apoptosis. It could also suppress cell tube formation, migration, and invasion. Moreover, TN-2 showed obvious antitumor effects on the PC-3 cell-derived xenograft model with negligible side effects and good pharmacokinetic profiles. These data demonstrate that TN-2 could be a promising dual-target chemotherapeutic agent for the treatment of prostate cancer.

Polyhydroquinoline derivatives for diabetic management: synthesis, in vitro and in silico approaches.

Background: Medication used to treat Type 2 diabetes by decreasing the absorption of carbohydrates in the intestine consists of α-glucosidase inhibitors. Polyhydroquinoline derivatives have attracted interest as excellent antidiabetic agents. Methods: Polyhydroquinoline derivatives (1-17) were synthesized and tested for in vitro α-glucosidase inhibitory activity. Results: All the synthesized compounds exhibited excellent to good inhibitory activity, having IC50 values from 1.23±0.03 to 73.85±0.61μM, compared with the standard drug, acarbose. The binding mechanism of these derivatives with α-glucosidase was deduced by docking studies and indicated that a slight variation in the orientation of compounds, affects their binding capability. Conclusion: In order to find new antidiabetic drugs, this study has discovered prospective lead candidates.

Exploring the synthesis, structure, spectroscopy and biological activities of novel 4-benzylidene-1-(2-(2,4-dichloro phenyl)acetyl) thiosemicarbazide derivatives: An integrated experimental and theoretical investigation

BackgroundNovel α-amylase inhibitors play a crucial role in managing diabetes and obesity, contributing to improved public health by addressing these challenging and prevalent conditions. Moreover, the synthesis of anti-oxidant agents is essential due to their potential in combating oxidative stress-related diseases and promoting overall health. ObjectiveSynthesis of thoisemicarbazone derivatives of 2,4-dichlorophenyl acetic acid and to screened them for their biological activities. MethodThiosemicarbazone derivatives (4–13) were synthesized by refluxing 2,4-dichlorophenyl acetic acid with sulfuric acid in ethanol to get the ester (2), which was further refluxed with thiosemicarbazide to get compound (3). Finally, different aromatic aldehydes were refluxed with compound (3) in ethanol in catalytic amount of acetic acid to obtained the final products (4–13). Using modern spectroscopic techniques including HR-ESI-MS, 13C-, and 1H NMR, the structures of the created derivatives were confirmed. ResultsThe synthesized derivatives showed excellent to good inhibitory activity in the range of IC50 values of 4.95 ± 0.44 to 69.71 ± 0.05 µM against α-amylase enzyme when compared to standard drug acarbose (IC50 = 21.55 ± 1.31 µM). In case of iron chelating activity, these products showed potent activity better than standard EDTA (IC50 = 66.43 ± 1.07 µM) in the range of IC50 values of 22.43 ± 2.09 to 61.21 ± 2.83 µM. However, the obtained products also show excellent to good activity in the range of IC50 values of 28.30 ± 1.17 to 64.66 ± 2.43 µM against hydroxyl radical scavenging activity when compared with standard vitamin C (IC50 = 60.51 ± 1.02 µM). DFT used to calculate different reactivity factors including ionization potential, electronegativity, electron affinity, chemical softness, and chemical hardness were calculated using frontier molecular orbital (FMO) computations. The molecular docking studies for the synthesized derivatives with α-amylase were carried out using the AutoDock Vina to understand the binding affinities with active sites of the protein.

Polymethoxyflavone from Citrus depressa as an inhibitor against various variants of SARS-CoV-2 spike protein

Ethnopharmacological relevanceIn traditional Taiwanese medicine, Citrus depressa Hayata serves as the raw material of Chen-Pi which has been widely used to treat respiratory ailments. Scientific investigations have validated the attributes of C. depressa, elucidating its valuable properties, including antioxidative, anti-inflammatory, anticancer, neuroprotion, hepatoprotection, and hypolipidemic effects. Aim of the studyThis study aims to isolate a universal inhibitor of the SARS-CoV-2 spike protein from C. depressa and confirm the mechanism by which these inhibitors disrupt the binding of the spike protein to hACE2. Materials and methodsThe whole fruit of C. depressa was subjected to ethanol extraction, following by partitioning to obtain water, butanol, and ethyl acetate fractions. To identify the inhibitory components in citrus fruits, we performed both the SPR assay and the SARS-CoV-2 pseudo-virus assays. Subsequently, we employed a bioassay-guided approach to efficiently isolate and characterize the bioactive constituents that hindered the interaction between the SARS-CoV-2 spike protein and hACE2, using a combination of MPLC and Semi-preparative HPLC for compound isolation. ELISA based spike protein binding assay evaluate the inhibitory activities of the extract and potential constituents against multiple spike protein variants. To further shed light on the inhibitory mechanism, candidate inhibitors were validated through the SPR assay and molecular docking. ResultsThe crude extract and ethyl acetate layer derived from C. depressa showed significant inhibitory activity on SARS-CoV-2 Omicron BA.4/5, with IC50 of 77.4 μg/mL and 100 μg/mL, respectively. Ten potential compounds from C. depressa have been identified with inhibitory activity against various SARS-CoV-2 spike proteins. 2′-hydroxy-4,4′,5′,6′-tetramethoxychalcone (Cd3) and 5-hydroxy-3′,4′,6,7,8-pentamethoxyflavone (Cd8) also showed good inhibitory activity to the spike protein, with KD of 0.79 μM and 37.3 nM, respectively. These findings are in line with prior study, indicating Cd3 and Cd8 can bind to key amino acid residue, disrupting the formation of the spike protein and h-ACE2 complex. ConclusionThis study presents the initial evidence showcasing the inhibitory effect of polymethoxyflavones (PMFs) on the spike protein of SARS-CoV-2. Moreover, the inhibitory activity of C. depressa extracts indicates their potential to prevent infections of different SARS-CoV-2 variants.

Discovery of N-(phenylsulfonyl)thiazole-2-carboxamides as potent α-glucosidase inhibitors.

In a search for novel nonsugar α-glucosidase inhibitors for diabetes treatment, a series of N-(phenylsulfonyl)thiazole-2-carboxamide derivatives were designed and synthesized, the α-glucosidase inhibitory activities were then evaluated. Several compounds with promising α-glucosidase inhibitory effects were identified. Among these, compound W24 which shows low cytotoxicity and good α-glucosidase inhibitory activity with an IC50 value of 53.0 ± 7.7 μM, is more competitive compared with the commercially available drug acarbose (IC50 = 228.3 ± 9.2 μM). W24 was identified as a promising candidate in the development of α-glucosidase inhibitors. Molecular docking studies and molecular dynamics simulation were also performed to reveal the binding pattern of the active compound to α-glucosidase, and the binding free energy of the best compound W24 was 36.3403 ± 3.91 kcal/mol.

Synthesis and Antifungal Activity of 2-(2-Benzoxazolyl)-1-arylethanone and 2-(2-Benzoxazolyl)-1-alkylethanone Derivatives.

To discover more effective antifungal candidates, 33 benzoxazole derivatives, were designed, synthesized, and evaluated for their antifungal activity against seven phytopathogenic fungi by the mycelium growth rate method. Among 33 benzoxazole derivatives had thirteen derivatives no reported, and new derivatives C17 exhibited good inhibitory activity against Phomopsis sp. with EC50 values of 3.26 μM. Structure-activity relationship (SAR) of these derivatives analysis indicated that the substituent played a key role in antifungal activity in ortho-, meta- and para- substituted acetophenones. The preliminary mechanistic exploration demonstrated that C17 might exert its antifungal activity by targeting the mycelia cell membrane, which was verified by the observed changes in mycelial morphology, the formation of extracellular polysaccharides, cellular contents, cell membrane permeability and integrity, among other effects. Furthermore, C17 had potent curative effect against Phomopsis sp. in vivo, which indicated that C17 may be as a novelty potent antifungal agent.

The immunomodulatory activity of Orthosiphon aristatus against atopic dermatitis: Evidence-based on network pharmacology and molecular simulations

ObjectivesTo explore the potential activity of Orthosiphon aristatus (OA) against atopic dermatitis (AD). MethodsPhytocompounds from OA were identified through chromatography analysis, then continued to target identification and functional annotation to explore the potential target of OA. Then, network pharmacology from annotated proteins determined protein targets for OA phytocompounds. Protein with highest rank according to the betweenness and closeness algorithm then continued to molecular docking and validated through molecular dynamics analysis. ResultsChromatography data analysis revealed thirty-six compounds, predominantly classified as carboxylic acid, fatty acyls, and polyphenols. Upon identifying these compounds, network biology-based target identification revealed their potential bioactivity in modulating inflammation in AD. Tumour Necrosis Factor-alpha (TNF-α) and Prostaglandin G/H synthase 2 (PTGS2) emerged as the most probable targets based on hub centrality in the protein–protein interaction network. Later, molecular docking analyses highlighted sixteen compounds with good inhibitory activity against these two proteins. Notably, molecular dynamics simulation revealed that three compounds out of the previous sixteen potential compounds were more likely to act as the TNF-α and PTGS2 inhibitor as well as their native inhibitor. Those compounds are (1R,9R)-5-Cyclohexyl-11- (propylsulfonyl)-7,11- diazatricyclo[7.3.1.02,7]trideca- 2,4-dien-6-one, also known as ZINC8297940, as the best TNF-α inhibitor along with dl-Leucineamide and Benazol P as the potential inhibitor of PTGS2. ConclusionsThese findings suggest that OA may exert therapeutic effects against AD by controlling inflammation through TNF-α and PTGS2 signalling pathways.

Discovery of 4-hydroxyl pyrazole derivatives as potent ferroptosis inhibitors

Ferroptosis, an iron-dependent form of regulated cell death, has been well recognized as a pathogenic mechanism in driving many diseases, such as neurodegenerative disorders, ischemia-reperfusion (I/R) injury. Blocking ferroptosis has been emerging as a feasible therapeutic strategy for the prevention and treatment of these diseases. However, novel potent ferroptosis inhibitors remain to be developed for further clinical applications. In this study, we screened our in-house compound libraries by phenotypic assays and identified a 4-hydroxyl pyrazole derivative HW-3 with good ferroptosis inhibitory activity (EC50 = 120.1 ± 3.5 nM). Based on the structure of HW-3, a series of 4-hydroxyl pyrazole derivatives were further designed and synthesized. Among these compounds, compound 25 could significantly inhibit RSL3-induced ferroptosis with an EC50 value of 8.6 ± 2.2 nM in HT-1080 cells, which was 3-fold more potent than the classical ferroptosis inhibitor ferrostatin-1 (Fer-1) (EC50 = 23.4 ± 1.3 nM). The potent ferroptosis inhibitory activity of compound 25 was further validated in multiple additional cell lines. Our mechanistic study revealed that compound 25 inhibited ferroptosis via intrinsic radical-trapping antioxidative capacity. Taken together, the findings of our study demonstrate 4-hydroxyl pyrazole derivative 25 is a potent ferroptosis inhibitor, which holds a great therapeutic potential for further development.

New Imidazo[1,2-a]pyridin-2-yl Derivatives as AChE, BChE, and LOX Inhibitors; Design, Synthesis, and Biological Evaluation

Background: Inhibition of cholinesterase enzyme has been recognized as an important target in the symptomatic treatment of Alzheimer’s disease. Objective: In the current work, a series of new N-(4-(imidazo[1,2-a]pyridin-2-yl)phenyl)cinnamamide derivatives were synthesized and their inhibitory activities against acetyl cholinesterase, butrylcholines terase, and Lipoxygenase were evaluated. Methods: The target compounds were synthesized as the literature reported with some modifications. The AChE, BChE, and LOX inhibitory activities of the synthesized compounds were evaluated using in vitro methods. The docking and kinetic studies were performed for the most potent compounds to evaluate the inhibition mechanism. Results: The structural elucidation of the synthesized imidazo-pyridine derivatives was performed by different spectroscopic techniques including IR, NMR, and Mass. Most of the synthesized compounds demonstrated good AChE, BChE, and LOX inhibitory activities. The most active AChE, BChE, and sLOX-1 inhibitors were found for compounds 4a, 4g, and 4l, respectively. The docking study also revealed that the three compounds, 4a, 4g, and 4l, have important binding interactions with the AChE, BChE, and sLOX-1 enzyme active sites, respectively. Conclusion: The results of current study shows imidazo[1,2-a]pyridine derivatives have potential for development of novel drug candidate for AD as AChE, BChE and sLOX-1 inhibitors.

Promising inhibition of diabetes-related enzymes and antioxidant properties of Ptilostemon casabonae leaves extract

Type 2 diabetes (T2D) is a progressive metabolic disorder of glucose metabolism. One of the therapeutic approaches for the treatment of T2D is reducing postprandial hyperglycaemia through inhibition of the digestive enzymes α-glucosidase and α-amylase. In this context, aimed at identifying natural products endowed with anti-T2D potential, we focused on Ptilostemon casabonae (L.) Greuter, a species belonging to Asteraceae family. Enzymatic inhibition, antioxidant activity, phenolic composition and cellular assays were performed. This study revealed that the P. casabonae hydroalcoholic extract exerts a potent inhibitory activity against α-glucosidase. This activity is supported by an antioxidant effect, preventing ROS formation in a stressed cellular system. HPLC-PDA-MS/MS analysis, revealed a complex polyphenolic fraction. Among the tested pure compounds, 1,5-dicaffeoylquinic acid, apigenin and rutin displayed good α-glucosidase inhibitory activity. Our study suggested new potential of P. casabonae encouraging us to further testing the possible therapeutic potential of this extract.

Design and synthesis of certain 7-Aryl-2-Methyl-3-Substituted Pyrazolo{1,5-a}Pyrimidines as multikinase inhibitors

Four new series 7a-e, 8a-e, 9a-e, and 10a-e of 7-aryl-3-substituted pyrazolo[1,5-a]pyrimidines were synthesized and tested for their RTK and STK inhibitory activity. Compound 7d demonstrated potent enzymatic inhibitory activity against TrkA and ALK2 with IC50 0.087and 0.105 μM, respectively, and potent antiproliferative activity against KM12 and EKVX cell lines with IC50 0.82 and 4.13 μM, respectively. Compound 10e showed good enzyme inhibitory activity against TrkA, ALK2, c-KIT, EGFR, PIM1, CK2α, CHK1, and CDK2 in submicromolar values. Additionally 10e revealed antiproliferative activity against MCF7, HCT116 and EKVX with IC50 3.36, 1.40 and 3.49 μM, respectively; with good safety profile. Moreover, 10e showed cell cycle arrest at the G1/S phase and G1 phase in MCF7 and HCT116 cells with good apoptotic effect. Molecular docking studies were fulfilled for compound 10e and illustrated good interaction with the hot spots of the active site of the tested enzymes.

Unveiling the phytochemical profile, in vitro bioactivities evaluation, in silico molecular docking and ADMET study of essential oil from Clinopodium nepeta grown in Middle Atlas of Morocco

Clinopodium nepeta is an aromatic species appertaining to the Lamiaceae family, and has been mentioned for its numerous traditional uses and pharmacological properties, especially its antiradical and antimicrobial effects. The phytochemical profile of the aerial part essential oil via gas chromatography-mass spectrometry (GC-MS) technique identified 76.79 % of oxygenated monoterpenes, followed by monoterpene hydrocarbons (18.65 %), and sesquiterpene hydrocarbons (2.76 %). The main constituents were 1,8-cineole (22.80%), piperitenone oxide (14.78%), and limonene (10.73%). The tested oil revealed a good inhibitory activity on α-amylase and α-glucosidase with IC50 values of 3.66 ± 0.07 mg/mL and 3.009 ± 0.02 mg/mL, respectively. In addition, antibacterial data revealed that Clinopodium nepeta essential oil (CNEO) was active against a panel of pathogenic microorganisms, mainly Bacillus subtilis (17.53 ± 0.81 mm) and Bacillus cereus (16.19 ± 0.30 mm). Besides, CNEO showed interesting anticandidal effect against Candida albicans and Candida tropicalis. Moreover, the studied EO hold a great scavenging actvity against ABTS radical (IC50 = 571.2 ± 6.89 μg/mL) and remarkable protective effect on lipid peroxidation (IC50 = 714.61 ± 7.96 μg/mL). Besides, a strong total antioxidant ability (TAA = 283.16 ± 0.02 mg AAE/g E) at minimal dilution (1/10) was observed. Interestingly, docking and ADME (absorption, distribution, metabolism and excretion)-associated physicochemical and pharmacokinetic effects were evaluated to promote the in vitro outcomes. This investigation revealed the prevailing properties of CNEO, especially antioxidant, antibacterial, anticandidal, and antidiabetic potentials, and allow the development of natural and effective agents with high safety for public health.

Green synthesis and anti-tumor efficacy via inducing pyroptosis of novel 1H-benzo[e]indole-2(3H)-one spirocyclic derivatives

Pyroptosis induction is anticipated to be a new approach to developing anti-tumor medications. A novel class of spirocyclic compounds was designed by hybridization of 1H-Benzo[e]indole-2(3H)-one with 1,4-dihydroquinoline and synthesized through a new green “one-pot” synthesis method using 10 wt% SDS/H2O as a solvent to screen novel tumor cell pyroptosis inducers. The anti-tumor activity of all compounds in vitro was determined by the MTT method, and a fraction of the compounds showed good cell growth inhibitory activity. The quantitative structure–activity relationship models of the compounds were established by artificial intelligence random forest algorithm (R2 = 0.9656 and 0.9747). The ideal compound A9 could, in a concentration-dependent manner, prevent ovarian cancer cells from forming colonies, migrating, and invading. Furthermore, A9 could significantly induce pyroptosis and upregulate the expression of pyroptosis-related proteins GSDME-N, in addition to inducing apoptosis and mediating the expression of apoptosis-related proteins in ovarian cancer cells. A9 (5 mg/kg) significantly reduced tumor volume and weight of ovarian cancer in vivo, decreased caspase-3 expression in tumor tissue, and induced the production of GSDME-N. This study provides a green and efficient atom-economic synthesis method for 1H-Benzo[e]indole-2(3H)-one spirocyclic derivatives and a promising pyroptosis inducer with anti-tumor activity.

Phytochemical analysis, in vitro and in silico effects from Alstonia boonei De Wild stem bark on selected digestive enzymes and adipogenesis in 3T3-L1 preadipocytes

BackgroundObesity is a global health issue arising from the unhealthy accumulation of fat. Medicinal plants such as Alstonia boonei stem bark has been reported to possess body weight reducing effect in obese rats. Thus, this study sought to investigate the in vitro and in silico effects of fractions from Alstonia boonei stem bark on selected obesity-related digestive enzymes and adipogenesis in 3T3-L1 preadipocytes.MethodTwo fractions were prepared from A. boonei: crude alkaloid fraction (CAF) and crude saponin fraction (CSF), and their phytochemical compounds were profiled using Liquid chromatography with tandem mass spectrometry (LCMS/MS). The fractions were assayed for inhibitory activity against lipase, α-amylase and α-glucosidase, likewise their antiadipogenic effect in 3T3-L1 adipocytes. The binding properties with the 3 enzymes were also assessed using in silico tools.ResultsEleven alkaloids and six saponin phytochemical compounds were identified in the CAF and CSF using LCMS/MS. The CAF and CSF revealed good inhibitory activity against pancreatic lipase enzyme, but weak and good activity against amylase respectively while only CSF had inhibitory activity against α-glucosidase. Both fractions showed antiadipogenic effect in the clearance of adipocytes and reduction of lipid content in 3T3-L1 adipocytes. The LCMS/MS identified compounds (41) from both fractions demonstrated good binding properties with the 3 enzymes, with at least the top ten compounds having higher binding energies than the reference inhibitors (acarbose and orlistat). The best two docked compounds to the three enzymes were firmly anchored in the substrate binding pockets of the enzymes. In a similar binding pattern as the reference acarbose, Estradiol-17-phenylpropionate (-11.0 kcal/mol) and 3α-O-trans-Feruloyl-2 α -hydroxy-12-ursen-28-oic acid (-10.0 kcal/mol) interacted with Asp197 a catalytic nucleophile of pancreatic amylase. Estradiol-17-phenylpropionate (-10.8 kcal/mol) and 10-Hydroxyyohimbine (-10.4 kcal/mol) interacted with the catalytic triad (Ser152-Asp176-His263) of pancreatic lipase while Estradiol-17-phenylpropionate (-10.1 kcal/mol) and 10-Hydroxyyohimbine (-9.9 kcal/mol) interacted with Asp616 and Asp518 the acid/base and nucleophilic residues of modelled α-glucosidase.ConclusionThe antiobesity effect of A. boonei was displayed by both the alkaloid and saponin fractions of the plant via inhibition of pancreatic lipase and adipogenesis.

Synthesis and characterization of novel chitosan derivatives (containing dipyridinium quaternary salts) with antimicrobial potential

Chitosan derivatives are versatile materials, biocompatible and biodegradable, that can be tailor-made to suit specific biomedical applications. In this study, two N-heterocyclic salts (N,N′-diphenacyl-[4,4′-dipyridinium] dibromide (DP) and N,N′-diphenacyl-1,2-bis-(4-pyridinium)ethane dibromide (DPE)) were used for chitosan functionalization to enhance its antimicrobial potential. Physico-chemical characterization of the newly synthesized derivatives (Ch-DP and Ch-DPE) was performed by elemental analysis, spectrometry (UV–Vis, FTIR), electrochemistry (OCP, CV), and electron microscopy (SEM) proving that the highest degree of functionalization was obtained for Ch-DP. The antimicrobial effect of chitosan functionalization was further tested in terms of its interaction with Listeria monocytogenes Scott A, and Staphylococcus aureus ATCC 25923, as Gram-positive bacteria and Escherichia coli ATCC 25922, as Gram-negative bacterium, respectively, showing that the Ch-DP had a good inhibitory activity compared with Ch-DPE.

Comparative genomics reveals environmental adaptability and antimicrobial activity of a novel Streptomyces isolated from soil under black Gobi rocks.

A novel Streptomyces strain, designated 3_2T, was isolated from soil under the black Gobi rock sample of Northwest China. The taxonomic position of this strain was revealed by a polyphasic approach. Comparative analysis of the 16S rRNA gene sequences indicated that 3_2T was closely related to the members of the genus Streptomyces, with the highest similarity to Streptomyces rimosus subsp. rimosus CGMCC 4.1438 (99.17%), Streptomyces sioyaensis DSM 40032 (98.97%). Strain 3_2T can grow in media up to 13% NaCl. The genomic DNA G + C content of strain 3_2T was 69.9%. We obtained the genomes of 22 Streptomyces strains similar to strain 3_2T, compared the average nucleotide similarity, dDDH and average amino acid identity, and found that the genomic similarity of the new isolate 3_2T to all strains was below the threshold for interspecies classification. Chemotaxonomic data revealed that strain 3_2T possessed MK-9 (H6) and MK-9 (H8) as the major menaquinones. The cell wall contained LL-diaminopimelic acid (LL-DAP) and the whole-cell sugars were ribose and glucose. The major fatty acid methyl esters were iso-C16:0 (23.6%) and anteiso-C15:0 (10.4%). The fermentation products of strain 3_2T were inhibitory to Staphylococcus aureus and Bacillus thuringiensi. The genome of 3_2T was further predicted using anti-smash and the strain was found to encode the production of 41 secondary metabolites, and these gene clusters may be key to the good inhibitory activity exhibited by the strain. Genomic analysis revealed that strain 3_2T can encode genes that produce a variety of genes in response to environmental stresses, including cold shock, detoxification, heat shock, osmotic stress, oxidative stress, and these genes may play a key role in the harsh environment in which the strain can survive. Therefore, this strain represents a novel Streptomyces species, for which the name Streptomyces halobius sp. nov. is proposed. The type strain is 3_2T (= JCM 34935T = GDMCC 4.217T).