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1.
Katharigatta N. Venugopala Sandeep Chandrashekharappa Pran Kishore Deb Christophe Tratrat Melendhran Pillay Deepak Chopra Nizar A. Al-Shari Wafa Hourani Lina A. Dahabiyeh Pobitra Borah Rahul D. Nagdeve Susanta K. Nayak Basavaraj Padmashali Mohamed A. Morsy Bandar E. Aldhubiab Mahesh Attimarad Anroop B. Nair Nagaraja Sreeharsha Michelyne Haroun Sheena Shashikanth Viresh Mohanlall Raghuprasad Mailavaram 《Journal of enzyme inhibition and medicinal chemistry》2021,36(1):1472
A series of 1,2,3-trisubstituted indolizines (2a–2f, 3a–3d, and 4a–4c) were screened for in vitro whole-cell anti-tubercular activity against the susceptible H37Rv and multidrug-resistant (MDR) Mycobacterium tuberculosis (MTB) strains. Compounds 2b–2d, 3a–3d, and 4a–4c were active against the H37Rv-MTB strain with minimum inhibitory concentration (MIC) ranging from 4 to 32 µg/mL, whereas the indolizines 4a–4c, with ethyl ester group at the 4-position of the benzoyl ring also exhibited anti-MDR-MTB activity (MIC = 16–64 µg/mL). In silico docking study revealed the enoyl-acyl carrier protein reductase (InhA) and anthranilate phosphoribosyltransferase as potential molecular targets for the indolizines. The X-ray diffraction analysis of the compound 4b was also carried out. Further, a safety study (in silico and in vitro) demonstrated no toxicity for these compounds. Thus, the indolizines warrant further development and may represent a novel promising class of InhA inhibitors and multi-targeting agents to combat drug-sensitive and drug-resistant MTB strains. 相似文献
2.
Tehreem Tahir Mirza Imran Shahzad Rukhsana Tabassum Muhammad Rafiq Muhammad Ashfaq Mubashir Hassan Katarzyna Kotwica-Mojzych Mariusz Mojzych 《Journal of enzyme inhibition and medicinal chemistry》2021,36(1):1509
In the present study, a series of azo derivatives (TR-1 to TR-9) have been synthesised via the diazo-coupling approach between substituted aromatic amines with phenol or naphthol derivatives. The compounds were evaluated for their therapeutic applications against alpha-glucosidase (anti-diabetic) and pathogenic bacterial strains E. coli (gram-negative), S. aureus (gram-positive), S. aureus (gram-positive) drug-resistant strain, P. aeruginosa (gram-negative), P. aeruginosa (gram-negative) drug-resistant strain and P. vulgaris (gram-negative). The IC50 (µg/mL) of TR-1 was found to be most effective (15.70 ± 1.3 µg/mL) compared to the reference drug acarbose (21.59 ± 1.5 µg/mL), hence, it was further selected for the kinetic studies in order to illustrate the mechanism of inhibition. The enzyme inhibitory kinetics and mode of binding for the most active inhibitor (TR-1) was performed which showed that the compound is a non-competitive inhibitor and effectively inhibits the target enzyme by binding to its binuclear active site reversibly. 相似文献
3.
Zhe Zhang Zhao-Sheng Zhang Xiao Wang Gao-Lei Xi Zhen Jin You-Zhi Tang 《Journal of enzyme inhibition and medicinal chemistry》2021,36(1):2087
Novel series of pleuromutilin analogs containing substituted 1,2,3-triazole moieties were designed, synthesised and assessed for their in vitro antibacterial activity against Methicillin-resistant Staphylococcus aureus (MRSA). Initially, the in vitro antibacterial activities of these derivatives against 4 strains of S. aureus (MRSA ATCC 43300, ATCC 29213, AD3, and 144) were tested by the broth dilution method. Most of the synthesised pleuromutilin analogs displayed potent activities. Among them, compounds 50, 62, and 64 (MIC = 0.5∼1 µg/mL) showed the most effective antibacterial activity and their anti-MRSA activity were further studied by the time-killing kinetics approach. Binding mode investigations by surface plasmon resonance (SPR) with 50S ribosome revealed that the selected compounds all showed obvious affinity for 50S ribosome (KD = 2.32 × 10−8∼5.10 × 10−5 M). Subsequently, the binding of compounds 50 and 64 to the 50S ribosome was further investigated by molecular modelling. Compound 50 had a superior docking mode with 50S ribosome, and the binding free energy of compound 50 was calculated to be −12.0 kcal/mol. 相似文献
4.
《Saudi Journal of Biological Sciences》2021,28(11):6532-6543
Thymus vulgaris L. (thyme), Origanum majorana L. (marjoram), and Origanum vulgare L. (oregano) were used to determine whether light modification (plants grown under nets with 40% shaded index or in un-shaded open field) could improve the quantity and quality of essential oils (EOs) and antioxidant activity. The yield of EOs of thyme, marjoram, and oregano obtained after 120 min of hydrodistillation was 2.32, 1.51, and 0.27 mL/100 g of plant material, respectively. At the same time under shading conditions plants synthetized more EOs (2.57, 1.68, and 0.32 mL/100 g of plant material). GC/MS and GC/FID analyses were applied for essential oils determinations. The main components of the thyme essential oil are thymol (8.05–9.35%); γ-terpinene (3.49–4.04%); p-cymene (2.80–3.60%) and caryophyllene oxide (1.54–2.15%). Marjoram main components were terpinene 4-ol (7.44–7.63%), γ-terpinene (2.82–2.86%) and linalool (2.04–2.65%) while oregano essential oil consisted of the following components: caryophyllene oxide (3.1–1.93%); germacrene D (1.17–2.0%) and (E)-caryophyllene (1.48–1.1%). The essential oil from thyme grown under shading (EC50 value after 20 min of incubation) have shown the highest antioxidant activity – 0.85 mg mL−1 in comparison to marjoram and oregano (shaded plants EC50 19.97 mg mL−1 and 7.02 mg mL−1 and unshaded, control plants EC50 54.01 mg mL−1 and 7.45 mg mL−1, respectively). The medicinal plants are a good source of natural antioxidants with potential application in the food and pharmaceutical industries. For production practice, it can be recommended to grow medicinal plants in shading conditions to achieve optimal quality parameters. 相似文献
5.
Shew-Meei Sheu Hsin Cheng Cheng-Ye Kao Yao-Jong Yang Jiunn-Jong Wu Bor-Shyang Sheu 《Journal of biomedical science》2014,21(1)
Background
Hyperglycemia increases the risk of gastric cancer in H. pylori-infected patients. High glucose could increase endothelial permeability and cancer-associated signaling. These suggest high glucose may affect H. pylori or its infected status.We used two strains to investigate whether H. pylori growth, viability, adhesion and CagA-phosphorylation level in the infected-AGS cells were influenced by glucose concentration (100, 150, and 200 mg/dL).Results
The growth curves of both strains in 200 mg/dL of glucose were maintained at the highest optimal density after 48 h and the best viability of both strains were retained in the same glucose condition at 72 h. Furthermore, adhesion enhancement of H. pylori was significantly higher in 200 mg/dL of glucose as compared to that in 100 and 150 mg/dL (p < 0.05). CagA protein also increased in higher glucose condition. The cell-associated CagA and phosphorylated-CagA was significantly increased in 150 and 200 mg/dL of glucose concentrations as compared to that of 100 mg/dL (p < 0.05), which were found to be dose-dependent.Conclusion
Higher glucose could maintain H. pylori growth and viability after 48 h. H. pylori adhesion and CagA increased to further facilitate the enhancement of cell-associated CagA and phosphorylated CagA in higher glucose conditions. 相似文献6.
Seyed Reza Najafizadeh Zaniar Ghazizadeh Arash Aghajani Nargesi Masoud Mahdavi Shabnam Abtahi Hossein Mirmiranpour Manouchehr Nakhjavani 《Cell stress & chaperones》2015,20(3):537-543
Heat shock proteins (HSPs) have been repeatedly implicated in the pathogenesis of rheumatoid arthritis (RA). The authors aimed to study applicability of heat shock protein 70 (HSPA1A) serum levels as a diagnostic factor and a severity indicator in patients with RA and to quantify cut-off point that predicts status of RA with highest specificity. A total of 76 patients with RA and 36 healthy adults were studied in this case-control analysis. Patients had a higher HSPA1A level than the control group (0.78 ± 0.13 vs. 0.12 ± 0.02 ng/mL, p = 0.006), irrespective of presence of absence of rheumatoid factor or anti-citrullinated cyclic peptide. Next, diagnostic accuracy of the HSPA1A in diagnosis of RA was evaluated (area under curve 0.71; p < 0.05). HSPA1A predicted status of having RA in levels above 0.42 ng/mL with more than 90 % specificity. In addition to diagnostic value, HSPA1A can distinguish between high disease activity (1.66 ± 0.75 ng/mL) and low (0.49 ± 0.1 ng/mL), moderate (0.52 ± 0.12 ng/mL), or remission phase (0.48 ± 0.11 ng/mL). Moreover, patients in remission still had a higher HSPA1A level compared to normal subject (0.48 ± 0.11 vs. 0.12 ± 0.02 ng/mL, p < 0.05). Our results showed that serum HSPA1A could be implemented as a specific tool to facilitate diagnosis and monitoring disease activity in patients with rheumatoid arthritis.
Electronic supplementary material
The online version of this article (doi:10.1007/s12192-015-0578-z) contains supplementary material, which is available to authorized users. 相似文献7.
Zul Kamal Farhat Ullah Muhammad Ayaz Abdul Sadiq Sajjad Ahmad Anwar Zeb Abid Hussain Muhammad Imran 《Biological research》2015,48(1)
Background
Atriplex laciniata L. was investigated for phenolic, flavonoid contents, antioxidant, anticholinesterase activities, in an attempt to explore its effectiveness in Alzheimer’s and other neurological disorders. Plant crude methanolic extract (Al.MeF), subsequent fractions; n-hexane (Al.HxF), chloroform (Al.CfF), ethyl acetate (Al.EaF), aqueous (Al.WtF), Saponins (Al.SPF) and Flavonoids (Al.FLVF) were investigated for DPPH, ABTS and H2O2 free radical scavenging activities. Further these extracts were subjected to acetylcholinesterase (AChE) & butyrylcholinesterase (BChE) inhibitory activities using Ellman’s assay. Phenolic and Flavonoid contents were determined and expressed in mg Gallic acid GAE/g and Rutin RTE/g of samples respectively.Results
In DPPH free radicals scavenging assay, Al.FLVF, Al.SPF and Al.MeF showed highest activity causing 89.41 ± 0.55, 83.37 ± 0.34 and 83.37 ± 0.34% inhibition of free radicals respectively at 1 mg/mL concentration. IC50 for these fractions were 33, 83 and 82 μg/mL respectively. Similarly, plant extracts showed high ABTS scavenging potential, i.e. Al.FLVF (90.34 ± 0.55), Al.CfF (83.42 ± 0.57), Al.MeF (81.49 ± 0.60) with IC50 of 30, 190 and 70 μg/ml respectively. further, H2O2 percent scavenging was highly appraised in Al.FLVF (91.29 ± 0.53, IC50 75), Al.SPF (85.35 ± 0.61, IC50 70) and Al.EaF (83.48 ± 0.67, IC50 270 μg/mL). All fractions exhibited concentration dependent AChE inhibitory activity as; Al.FLVF, 88.31 ± 0.57 (IC50 70 μg/mL), Al.SPF, 84.36 ± 0.64 (IC50 90 μg/mL), Al.MeF, 78.65 ± 0.70 (IC50 280 μg/mL), Al.EaF, 77.45 ± 0.46 (IC50 270 μg/mL) and Al.WtF 72.44 ± 0.58 (IC50 263 μg/mL) at 1 mg/mL. Likewise the percent BChE inhibitory activity was most obvious in Al.FLVF 85.46 ± 0.62 (IC50 100 μg/mL), Al.CfF 83.49 ± 0.46 (IC50 160 μg/mL), Al.MeF 82.68 ± 0.60 (IC50 220 μg/mL) and Al.SPF 80.37 ± 0.54 (IC50 120 μg/mL).Conclusions
These results stipulate that A. laciniata is enriched with phenolic and flavonoid contents that possess significant antioxidant and anticholinestrase effects. This provide pharmacological basis for the presence of compounds that may be effective in Alzheimer’s and other neurological disorders. 相似文献8.
Badreddine Ben Slimane Olfa Ezzine Samir Dhahri Mohamed Lahbib Ben Jamaa 《Biological research》2014,47(1)
Background
Essential oils extracted from aromatic and medicinal plants have many biological properties and are therefore an alternative to the use of synthetic products. The chemical composition of essential oils from two medicinal plants (Eucalyptus globulus and E. lehmannii) was determined and, their insecticidal effects on the third and fourth larval stages of Orgyia trigotephras were assessed.Results
Larvae were collected from Jebel Abderrahmane (North-East of Tunisia), conserved in groups of 50/box (21 × 10 × 10 cm) at a temperature of 25°C. Larvae were tested for larvicidal activities of essential oils. Each oil was diluted in ethanol (96%) to prepare 3 test solutions (S1 = 0.05%, S2 = 0.10% and S3 = 0.50%). Essential oils were used for contact, ingestion and Olfactory actions and compared to reference products (Bacillus thuringiensis and Decis). Olfactory action of essential oils shows that larvae mortality is higher than contact action, lower than ingestion action. MTM and FTM of S3 of E. lehmannii were respectively 1 h 32 min and 1 h 39 min are higher than those of E. globulus (MTM = 51 min and FTM = 1 h 22 min 34 sec). Contact action of E. lehmannii oil shows low insecticidal activity compared to E. globulus. MTM are respectively (1 min 52 sec and 1 min 7 sec), FTM are (2 min 38 sec, 1 min 39 sec), are the shortest recorded for S3, on the third stage of larvae. The fourth stage of larvae, MTM are (2 min 20 sec and 2 min 9 sec), FTM are (3 min 25 sec, 3 min 19 sec). Ingestion action of essential oils is longer than the contact action, since the time of death exceeds 60 minutes for all species.Conclusion
Results shows that essential oils have a toxic action on nerves leading to a disruption of vital system of insects. High toxic properties make these plant-derived compounds suitable for incorporation in integrated pest management programs. 相似文献9.
Jae Ho Han Chang-Hee Suh Ju-Yang Jung Jin-Young Nam Jee Eun Kwon Hyunee Yim Hyoun-Ah Kim 《Arthritis research & therapy》2015,17(1)
IntroductionC-X-C motif chemokine 10 (CXCL10) is produced in response to interferon-γ, and tumor necrosis factor-α (TNF-α) triggers the accumulation of activated lymphocytes. CXCL13 is constitutively expressed in secondary lymphoid tissues, and the expression is upregulated by TNF-α, via T cell stimulation. It appears that CXCL10 and CXCL13 could play a potential role in the pathogenesis of adult-onset Still’s disease (AOSD), therefore, we investigated the associations between CXCL10 and CXCL13 levels and clinical manifestations in patients with active AOSD.MethodsBlood samples were collected from 39 active AOSD patients, 32 rheumatoid arthritis (RA) patients and 40 healthy controls (HC). Of the AOSD patients, follow-up samples were collected from 15 9.6 ± 9.2 months later. Serum levels of CXCL10 and CXCL13 were determined using enzyme-linked immunosorbent assay. CXCL10, CXCL13, and C-X-C chemokine receptor type 3 (CXCR3) expression levels in biopsy specimens obtained from 26 AOSD patients with skin rashes were investigated via immunohistochemistry.ResultsThe CXCL10 levels in AOSD patients (1,031.3 ± 2,019.6 pg/mL) were higher than in RA (146.3 ± 91.4 pg/mL, p = 0.008) and HC (104.4 ± 47.9 pg/mL, p = 0.006). Also, the CXCL13 levels of AOSD patients (158.8 ± 151.2 pg/mL) were higher than those of RA (54.4 ± 61.1 pg/mL, p < 0.001) and HC (23.5 ± 18.1 pg/mL, p < 0.001). Serum CXCL10 levels correlated with ferritin and systemic scores. Serum CXCL13 levels correlated with those of hemoglobin, C-reactive protein, ferritin, and albumin, and systemic scores. In follow-up AOSD patients, the levels of CXCL10 and CXCL13 fell significantly (153.7 ± 130.1 pg/mL, p = 0.002, and 89.1 ± 117.4 pg/mL, p = 0.001, respectively). On immunohistochemistry, the percentages of inflammatory cells expressing CXCL10 ranged from 1 to 85 %, CXCL13 from 1 to 72 %, and CXCR3 from 2 to 65 %. The percentage of CXCL10-positive inflammatory cells was higher in skin biopsy samples exhibiting mucin deposition than in those that did not (p = 0.01). CXCL13 levels were correlated with those of CD4 and CD68.ConclusionsSerum CXCL10 and CXCL13 levels may serve as clinical markers for assessment of disease activity in AOSD. CXCL10/CXCR3 and CXCL13 may contribute to the inflammatory response, especially skin manifestations thereof, in AOSD.
Electronic supplementary material
The online version of this article (doi:10.1186/s13075-015-0773-4) contains supplementary material, which is available to authorized users. 相似文献10.
Linalyl Acetate Is Metabolized by Pseudomonas incognita with the Acetoxy Group Intact 总被引:3,自引:1,他引:2
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Metabolism of linalyl acetate by Pseudomonas incognita isolated by enrichment culture on the acyclic monoterpene alcohol linalool was studied. Biodegradation of linalyl acetate by this strain resulted in the formation of linalool, linalool-8-carboxylic acid, oleuropeic acid, and Δ5-4-acetoxy-4-methyl hexenoic acid. Cells adapted to linalyl acetate metabolized linalyl acetate-8-aldehyde to linalool-8-carboxylic acid, linalyl acetate-8-carboxylic acid, Δ5-4-acetoxy-4-methyl hexenoic acid, and geraniol-8-carboxylic acid. Resting cell suspensions previously grown with linalyl acetate oxidized linalyl acetate-8-aldehyde to linalyl acetate-8-carboxylic acid, Δ5-4-acetoxy-4-methyl hexenoic acid, and pyruvic acid. The crude cell-free extract (10,000 g of supernatant), obtained from the sonicate of linalyl acetate-grown cells, was shown to contain enzyme systems responsible for the formation of linalyl acetate-8-carboxylic acid and linalool-8-carboxylic acid from linalyl acetate. The same supernatant contained NAD-linked alcohol and aldehyde dehydrogenases involved in the formation of linalyl acetate-8-aldehyde and linalyl acetate-8-carboxylic acid, respectively. On the basis of various metabolites isolated from the culture medium, resting cell experiments, growth and manometric studies carried out with the isolated metabolites as well as related synthetic analogs, and the preliminary enzymatic studies performed with the cell-free extract, a probable pathway for the microbial degradation of linalyl acetate with the acetoxy group intact is suggested. 相似文献
11.
Maria M. C. da Silva Jos B. de Araújo-Neto Ana C. J. de Araújo Priscilla R. Freitas Cícera D. de M. Oliveira-Tintino Iêda M. Begnini Ricardo A. Rebelo Luiz E. da Silva Sandro L. Mireski Michele C. Nasato Maria I. L. Krautler Jaime Ribeiro-Filho Henrique D. M. Coutinho Saulo R. Tintino 《Indian journal of microbiology》2021,61(1):100
This study aimed to evaluate the intrinsic antibacterial activity and antibiotic-enhancing effect of an arylamino methylene derivative (MAD) in association with fluoroquinolones. The antibacterial activity against multiresistant Pseudomonas aeruginosa, Staphylococcus aureus and Escherichia coli was analyzed by determining the minimum inhibitory concentration (MIC) using the broth micro dilution method. A reduction in the MIC of the fluoroquinolones against strains treated simultaneously with the MAD was interpreted as an enhanced antibiotic activity. While the MAD exhibited no clinically effective action (MIC ≥ 1.024 µg/mL), it was found to significantly potentiate the activity of norfloxacin, ofloxacin and lomefloxacin against all the strains, which may be related to structural similarities between the MAD and quinolones. Our findings suggest that Meldrum’s acid arylamino derivatives may represent promising molecules in the elaboration of new drugs to reverse resistance to fluoroquinolones. 相似文献
12.
Sevil Korkmaz Ayhan Atmanli Shiliang Li Tamás Radovits Peter Heged?s Enik? Barnucz Kristóf Hirschberg Sivakkanan Loganathan Yutaka Yoshikawa Hiroyuki Yasui Matthias Karck Gábor Szabó 《Experimental biology and medicine (Maywood, N.J.)》2015,240(9):1247-1255
The pathophysiology of ischemic myocardial injury involves cellular events, reactive oxygen species, and an inflammatory reaction cascade. The zinc complex of acetylsalicylic acid (Zn(ASA)2) has been found to possess higher anti-inflammatory and lower ulcerogenic activities than acetylsalicylic acid (ASA). Herein, we studied the effects of both ASA and Zn(ASA)2 against acute myocardial ischemia. Rats were pretreated with ASA (75 mg/kg) or Zn(ASA)2 (100 mg/kg) orally for five consecutive days. Isoproterenol (85 mg/kg, subcutaneously [s.c.]) was applied to produce myocardial infarction. After 17–22 h, animals were anesthetized with sodium pentobarbital (60 mg/kg, intraperitoneally [i.p.]) and both electrical and mechanical parameters of cardiac function were evaluated in vivo. Myocardial histological and gene expression analyses were performed. In isoproterenol-treated rats, Zn(ASA)2 treatment normalized significantly impaired left-ventricular contractility index (Emax 2.6 ± 0.7 mmHg/µL vs. 4.6 ± 0.5 mmHg/µL, P < 0.05), increased stroke volume (30 ± 3 µL vs. 50 ± 6 µL, P < 0.05), decreased systemic vascular resistance (7.2 ± 0.7 mmHg/min/mL vs. 4.2 ± 0.5 mmHg/min/mL, P < 0.05) and reduced inflammatory infiltrate into the myocardial tissues. ECG revealed a restoration of elevated ST-segment (0.21 ± 0.03 mV vs. 0.09 ± 0.02 mV, P < 0.05) and prolonged QT-interval (79.2 ± 3.2 ms vs. 69.5 ± 2.5 ms, P < 0.05) by Zn(ASA)2. ASA treatment did not result in an improvement of these parameters. Additionally, Zn(ASA)2 significantly increased the mRNA-expression of superoxide dismutase 1 (+73 ± 15%), glutathione peroxidase 4 (+44 ± 12%), and transforming growth factor (TGF)-β1 (+102 ± 22%). In conclusion, our data demonstrate that oral administration of zinc and ASA in the form of bis(aspirinato)zinc(II) complex is superior to ASA in preventing electrical, mechanical, and histological changes after acute myocardial ischemia. The induction of antioxidant enzymes and the anti-inflammatory cytokine TGF-β1 may play a pivotal role in the mechanism of action of Zn(ASA)2. 相似文献
13.
Frans A Kuypers Christina A Rostad Evan J Anderson Ann Chahroudi Preeti Jaggi Jens Wrammert Grace Mantus Rajit Basu Frank Harris Bradley Hanberry Andres Camacho-Gonzalez Shaminy Manoranjithan Miriam Vos Lou Ann Brown Claudia R Morris 《Experimental biology and medicine (Maywood, N.J.)》2021,246(23):2543
Secretory phospholipase 2 (sPLA2) acts as a mediator between proximal and distal events of the inflammatory cascade. Its role in SARS-CoV-2 infection is unknown, but could contribute to COVID-19 inflammasome activation and cellular damage. We present the first report of plasma sPLA2 levels in adults and children with COVID-19 compared with controls. Currently asymptomatic adults with a history of recent COVID-19 infection (≥4 weeks before) identified by SARS-CoV-2 IgG antibodies had sPLA2 levels similar to those who were seronegative (9 ± 6 vs.17 ± 28 ng/mL, P = 0.26). In contrast, children hospitalized with severe COVID-19 had significantly elevated sPLA2 compared with those with mild or asymptomatic SARS-CoV-2 infection (269 ± 137 vs. 2 ± 3 ng/mL, P = 0.01). Among children hospitalized with multisystem inflammatory syndrome in children (MIS-C), all had severe disease requiring pediatric intensive care unit (PICU) admission. sPLA2 levels were significantly higher in those with acute illness <10 days versus convalescent disease ≥10 days (540 ± 510 vs. 2 ± 1, P = 0.04). Thus, sPLA2 levels correlated with COVID-19 severity and acute MIS-C in children, implicating a role in inflammasome activation and disease pathogenesis. sPLA2 may be a useful biomarker to stratify risk and guide patient management for children with acute COVID-19 and MIS-C. Therapeutic compounds targeting sPLA2 and inflammasome activation warrant consideration. 相似文献
14.
Iron-based phosphorus chelator: Risk of iron deposition and action on bone metabolism in uremic rats
Wander Barros do Carmo Brbara Bruna Abreu Castro Luísa Cardoso Manso Priscylla Aparecida Vieira do Carmo Clvis Antnio Rodrigues Melani Ribeiro Custdio Vanda Jorgetti Helady Sanders-Pinheiro 《Experimental biology and medicine (Maywood, N.J.)》2022,247(5):446
Phosphate chelators are frequently used in patients with chronic kidney disease (CKD). New iron-based chelators remain understudied and offer a promising therapeutic option for the control of bone and mineral disorders of chronic kidney disease (BMD-CKD). We assessed the effect of the phosphorus chelator, chitosan-iron III (CH-FeCl), compared to calcium carbonate (CaCO3) in BMD-CKD and the potential iron overload in uremic rats. Thirty-two animals were divided into four groups, namely the control, CKD, CKD/CH-FeCl, and CKD/CaCO3 groups. CKD was induced by adding 0.75% (4 weeks) and 0.1% (3 weeks) adenine to the diet. The chelators were administered from week 3 through week 7. The renal function, BMD-CKD markers, and histomorphometry of the femur were assessed at week 7. The CKD group showed a significant increase in creatinine (83.9 ± 18.6 vs. 41.5 ± 22.1 µmol/L; P = 0.001), phosphate (3.5 ± 0.8 vs. 2.2 ± 0.2 mmol/L; P = 0.001), fractional excretion of phosphorus (FEP) (0.71 ± 0.2 vs. 0.2 ± 0.17; P = 0.0001), and FGF23 (81.36 ± 37.16 pg/mL vs. 7.42 ± 1.96; P = 0.011) compared to the control group. There was no accumulation of serum or bone iron after the use of CH-FeCl. The use of chelators reduced the FEP (control: 0.71 ± 0.20; CKD/CH-FeCl: 0.40 ± 0.16; CKD/CaCO3 0.34 ± 0.15; P = 0.001), without changes in the serum FGF23 and parathyroid hormone levels. Histomorphometry revealed the presence of bone disease with high remodeling in the uremic animals without changes with the use of chelators. The CH-FeCl chelator was efficient in reducing the FEP without iron accumulation, thereby paving the way for the use of this class of chelators in clinical settings in the future. 相似文献
15.
Background
Rumex species are traditionally used for the treatment of neurological disorders including headache, migraine, depression, paralysis etc. Several species have been scientifically validated for antioxidant and anticholinestrase potentials. This study aims to investigate Rumex hastatus D. Don crude methanolic extract, subsequent fractions, saponins and flavonoids for acetylcholinestrase, butyrylcholinestrase inhibition and diverse antioxidant activities to validate its folkloric uses in neurological disorders. Rumex hastatus crude methanolic extract (Rh. Cr), subsequent fractions; n-hexane (Rh. Hex), chloroform (Rh. Chf), ethyl acetate (Rh. EtAc), aqueous fraction (Rh. Aq), crude saponins (Rh. Sp) and flavonoids (Rh. Fl) were investigated against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) at various concentrations (125, 250, 500, 1000 μg/mL) using Ellman’s spectrophotometric analysis. Antioxidant potentials of Rh. Sp and Rh. Fl were evaluated using DPPH, H2O2 and ABTS free radical scavenging assays at 62.5, 125, 250, 500, 1000 μg/mL.Results
All the test samples showed concentration dependent cholinesterase inhibition and radicals scavenging activity. The AChE inhibition potential of Rh. Sp and Rh. Fl were most prominent i.e., 81.67 ± 0.88 and 91.62 ± 1.67 at highest concentration with IC50 135 and 20 μg/mL respectively. All the subsequent fractions exhibited moderate to high AChE inhibition i.e., Rh. Cr, Rh. Hex, Rh. Chf, Rh. EtAc and Rh. Aq showed IC50 218, 1420, 75, 115 and 1210 μg/mL respectively. Similarly, against BChE various plant extracts i.e., Rh. Sp, Rh. Fl, Rh. Cr, Rh. Hex, Rh. Chf, Rh. EtAc and Rh. Aq resulted IC50 165, 175, 265, 890, 92, 115 and 220 μg/mL respectively. In DPPH free radical scavenging assay, Rh. Sp and Rh. Fl showed comparable results with the positive control i.e., 63.34 ± 0.98 and 76.93 ± 1.13% scavenging at 1 mg/mL concentration (IC50 312 and 104 μg/mL) respectively. The percent ABTS radical scavenging potential exhibited by Rh. Sp and Rh. Fl (1000 μg/mL) were 82.58 ± 0.52 and 88.25 ± 0.67 with IC50 18 and 9 μg/mL respectively. Similarly in H2O2 scavenging assay, the Rh. Sp and Rh. Fl exhibited IC50 175 and 275 μg/mL respectively.Conclusion
The strong anticholinesterase and antioxidant activities of Rh. Sp, Rh. Fl and various fractions of R. hastatus support the purported ethnomedicinal uses and recommend R. hastatus as a possible remedy for the treatment of AD and neurodegenerative disorders. 相似文献16.
Elif Aye Erdoan Eliuz 《Indian journal of microbiology》2021,61(3):291
In this study, the aerial parts of Salvia hypargeia were subjected to hydrodistillation and the resulting compounds were analyzed in GC–MS. Antimicrobial activity of S. hypargeia essential oil (EO) against A. baumannii, S. aureus, and C. tropicalis were determined by agar well diffusion assay and microdilution method. Antimicrobial mechanism of the EO were investigated based on change of TTC-dehydrogenase relative, leakages of intracellular protein, DNA and potassium ion (K +). The main components of the EO were β-pinene, 1,8-cineole, camphor, α-pinene, 4-terpineol, and 4-thujanol. The MICs of the EO against the microorganisms were 15.2 mg/mL for S. aureus, 17.5 mg/mL for C. tropicalis and 28.8 mg/mL for A. baumannii. The inhibition zones were 18.16 mm, 25.01 mm, and 27.01 mm for A. baumannii, S. aureus, and C. tropicalis, respectively (p < 0.05). An increase in DNA, protein and K+ leakage was observed when microorganisms were exposed to the EO. The TTC-DRA of the treated microorganism cells was also significantly decreased because of slowing the respiration. The present study provided an experimental basis of practical application of S. hypargeia EO as a natural agent.Supplementary InformationThe online version contains supplementary material available at 10.1007/s12088-021-00939-1. 相似文献
17.
Khalid A. Agha Nader E. Abo-Dya Abdul Rashid Issahaku Clement Agoni Mahmoud E. S. Soliman Eatedal H. Abdel-Aal Zakaria K. Abdel-Samii Tarek S. Ibrahim 《Journal of enzyme inhibition and medicinal chemistry》2022,37(1):1241
An efficient method for synthesising NMDAR co-agonist Sunifiram (DM235), in addition to Sunifram-carbamate and anthranilamide hybrids, has been developed in high yields via protecting group-free stepwise unsymmetric diacylation of piperazine using N-acylbenzotiazole. Compounds 3f, 3d, and 3i exhibited promising nootropic activity by enhancing acetylecholine (ACh) release in A549 cell line. Moreover, the carbamate hybrid 3f was found to exhibit higher in vitro potency than donepezil with IC50 = 18 ± 0.2 nM, 29.9 ± 0.15 nM for 3f and donepezil, respectively. 3f was also found to effectively inhibit AChE activity in rat brain (AChE = 1.266 ng/mL) compared to tacrine (AChE = 1.137 ng/ml). An assessment of the ADMET properties revealed that compounds 3f, 3d, and 3i are drug-like and can penetrate blood–brain barrier. Findings presented here showcase highly potential cholinergic agents, with expected partial agonist activity towards glycine binding pocket of NMDAR which could lead to development and optimisation of novel nootropic drugs. 相似文献
18.
Chloe J Mitchell Gordon S Howarth Lauren C Chartier Debbie Trinder Ian C Lawrance Li San Huang Suzanne Mashtoub 《Experimental biology and medicine (Maywood, N.J.)》2020,245(18):1697
Crohn’s disease is a severe, incurable inflammatory bowel disease. Orally administered emu oil has demonstrated anti-inflammatory properties in previous models of gastrointestinal disease. We aimed to determine whether orally administered emu oil could attenuate disease in a mouse model of Crohn’s-like colitis. Female ARC(s) mice (CD-1 equivalent, n = 10/group) were intra-rectally administered water (120 μL) or trinitrobenzene sulfonic acid (TNBS; 3 mg in 50% ethanol; 120 μL bolus) on day 0. Mice were orally administered water (80 μL) or emu oil (80 μL or 160 μL) daily for five days and euthanized on day six. Bodyweight and disease activity were recorded daily. Colonoscopy, burrowing activity, facial grimace, histological parameters (damage severity, small intestinal villus height/crypt depth and colonic crypt depth), myeloperoxidase activity and intestinal permeability were assessed. P < 0.05 was considered statistically significant. TNBS decreased bodyweight (days 1, 2, 4; P < 0.05) and increased disease activity (days 1–6; P < 0.01), compared to normal controls. Emu oil (80 μL) attenuated disease activity on days 5–6 (P < 0.05), although bodyweight loss was not significantly impacted (P > 0.05). Facial grimace and colonoscopy scores were significantly increased in TNBS-control mice; effects attenuated by both volumes of emu oil (P < 0.001). TNBS increased histological damage severity compared to normal controls (P < 0.05); an effect attenuated by 80 μL emu oil (proximal and distal colon; P < 0.05) and 160 μL emu oil (distal colon; P < 0.01). In the ileum, villus height and crypt depth were unaffected by TNBS or emu oil treatment compared to normal (P > 0.05). TNBS-induced distal colonic crypt lengthening was unaffected following emu oil administration (P > 0.05). Remaining parameters, including burrowing, myeloperoxidase activity and intestinal permeability, were unchanged across all treatment groups (P > 0.05). In normal mice, emu oil treatment did not significantly impact any parameter compared to normal controls. In conclusion, emu oil reduced overall disease severity and facial grimace scores in TNBS mice. These results suggest therapeutic potential for orally administered emu oil in the management of Crohn’s disease. 相似文献
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Peng-Fei Zheng Zhuang Xiong Cui-ying Liao Xin Zhang Mei Feng Xiao-Zheng Wu Jing Lin Lin-Sheng Lei You-Cheng Zhang Shao-Hua Wang Xue-Tao Xu 《Journal of enzyme inhibition and medicinal chemistry》2021,36(1):1938
In this paper, bis (indol-3-yl) methanes (BIMs) were synthesised and evaluated for their inhibitory activity against α-glucosidase and α-amylase. All synthesised compounds showed potential α-glucosidase and α-amylase inhibitory activities. Compounds 5 g (IC50: 7.54 ± 1.10 μM), 5e (IC50: 9.00 ± 0.97 μM), and 5 h (IC50: 9.57 ± 0.62 μM) presented strongest inhibitory activities against α-glucosidase, that were ∼ 30 times stronger than acarbose. Compounds 5 g (IC50: 32.18 ± 1.66 µM), 5 h (IC50: 31.47 ± 1.42 µM), and 5 s (IC50: 30.91 ± 0.86 µM) showed strongest inhibitory activities towards α-amylase, ∼ 2.5 times stronger than acarbose. The mechanisms and docking simulation of the compounds were also studied. Compounds 5 g and 5 h exhibited bifunctional inhibitory activity against these two enzymes. Furthermore, compounds showed no toxicity against 3T3-L1 cells and HepG2 cells.
Highlights
- A series of bis (indol-3-yl) methanes (BIMs) were synthesised and evaluated inhibitory activities against α-glucosidase and α-amylase.
- Compound 5g exhibited promising activity (IC50 = 7.54 ± 1.10 μM) against α-glucosidase.
- Compound 5s exhibited promising activity (IC50 = 30.91 ± 0.86 μM) against α-amylase.
- In silico studies were performed to confirm the binding interactions of synthetic compounds with the enzyme active site.
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