scholarly journals CHARACTERIZATION OF MONOHEADED TRYPSIN INHIBITORS FROM THE SEEDS OF ABELMOSCHUS MOSCHATUS L.

2018 ◽  
Vol 11 (12) ◽  
pp. 459
Author(s):  
Muni Kumar Dokka ◽  
Hemalatha K. P. J ◽  
Siva Prasad Davuluri
Keyword(s):  
Chemical Modification ◽  
Mode Of Action ◽  
Physiological Role ◽  
Trypsin Inhibitors ◽  
Control Mechanisms ◽  
Bovine Trypsin ◽  
Ic50 Values ◽  
Arginine Residues ◽  
Inhibitory Activities

Objective: The objective of the present study was to characterize the monoheaded trypsin inhibitors, Abelmoschus moschatus trypsin inhibitor-I (AMTI-I) and AMTI-II from the seeds of A. moschatus with respect to their specificity, mode of action, and active site residues.Methods: Standard methods were followed in determining inhibitory activities of monoheaded inhibitors. IC50 values and inhibitory constants (Ki) of AMTI-I and AMTI-II were determined. Studies on complex formation and chemical modification of inhibitors were performed.Results: AMTI-I and AMTI-II were found to be serpins, strongly active against trypsin, moderately active against porcine elastase, Staphylococcus aureus protease, and Aspergillus oryzae protease. AMTI-I and AMTI-II have shown non-competitive type of inhibition toward bovine trypsin with Ki values of inhibitors for trypsin found to be 0.25±0.02 nM and 0.22±0.06 nM, respectively. Complex studies revealed the formation of stable 1:1 complex of trypsin with both AMTI-I and AMTI-II. Chemical modification of the functional groups of the inhibitors by selective reagents indicated that arginine residues are essential for their trypsin inhibitory activities.Conclusion: Investigations on the specificity of protease inhibitors are important for understanding their physiological role, control mechanisms involved in the regulation of proteolysis in biological systems and mode of action.

scholarly journals Optimizing model comparison for enzymatic mechanism analysis

2020 ◽  
Author(s):  
Ryan Walsh ◽  
Philippe Blain
Keyword(s):  
Model Comparison ◽  
Tyrosine Phosphatase ◽  
Enzyme Regulation ◽  
Physiological Role ◽  
Mechanism Analysis ◽  
Enzymatic Mechanism ◽  
Ic50 Values ◽  
Optimizing Model ◽  
Substrate Inhibitor

ABSTRACTCharacterization of enzyme inhibition in drug development is usually limited to a basic analysis with the classical inhibition models or simply the use of IC50 values. However, a better understanding of enzyme physiology and regulation is seen as key to unraveling and treating the processes associated with stubborn disease targets like Alzheimer’s disease. Recently it has been shown that enzyme regulation, through substrate, inhibitor or activator interactions can be modeled using the summation of binding curves. Here we examine the use of the modular equation permutations, that can be produced through binding curve summation, to fit and evaluate the interactions of abietic acid with protein tyrosine phosphatase nonreceptor type 11. This new sort of analysis will allow for improved insight into the physiological role enzymes play and the consequence their modulation may have in disease progression.

scholarly journals Characterization of Bioactivities and Biosynthesis of Angucycline/Angucyclinone Derivatives Derived from Gephyromycinifex aptenodytis gen. nov., sp. nov.

Marine Drugs ◽  
2021 ◽  
Vol 20 (1) ◽  
pp. 34
Author(s):  
Wen-Zhuo Zhu ◽  
Shu-Heng Wang ◽  
Hui-Min Gao ◽  
Ya-Ming Ge ◽  
Jun Dai ◽  
...  
Keyword(s):  
Chemical Structure ◽  
Polyketide Synthase ◽  
Emperor Penguin ◽  
Type Iii Polyketide Synthase ◽  
Cancerous Cell ◽  
The Family ◽  
Ic50 Values ◽  
Inhibitory Activities ◽  
The Antarctic

Strain NJES-13T is the type strain and currently the only species of the newly established actinobacteria genera Aptenodytes in the family Dermatophilaceae isolated from the gut microbiota of the Antarctic emperor penguin. This strain demonstrated excellent bioflocculation activity with bacteria-derived exopolysaccharides (EPSs). Moreover, it produced bioactive angucycline/angucyclinone derivatives (ADs) and contained one type III polyketide synthase (T3PKS), thus demonstrating great potential to produce novel bioactive compounds. However, the low productivity of the potential new AD metabolite was the main obstacle for its chemical structure elucidation. In this study, to increase the concentration of targeted metabolites, the influence of cellular morphology on AD metabolism in strain NJES-13T was determined using glass bead-enhanced fermentation. Based on the cellular ultra-structural observation driven by bacterial EPSs, and quantitative analysis of the targeted metabolites, the successful increasing of the productivity of three AD metabolites was achieved. Afterward, a new frigocyclinone analogue was isolated and then identified as 2-hydroxy-frigocyclinone, as well as two other known ADs named 2-hydroxy-tetrangomycin (2-HT) and gephyromycin (GPM). Three AD metabolites were found to demonstrate different bioactivities. Both C-2 hydroxyl substitutes, 2-hydroxy-tetrangomycin and 2-hydroxy-frigocyclinone, exhibited variable inhibitory activities against Staphylococcus aureus, Bacillus subtilis and Candida albicans. Moreover, the newly identified 2-hydroxy-frigocyclinone also showed significant cytotoxicity against three tested human-derived cancerous cell lines (HL-60, Bel-7402 and A549), with all obtained IC50 values less than 10 µM. Based on the genetic analysis after genomic mining, the plausible biogenetic pathway of the three bioactive ADs in strain NJES-13T was also proposed.

Insulinomimetic properties of trace elements and characterization of their in vivo mode of action

Diabetes ◽  
1990 ◽  
Vol 39 (10) ◽  
pp. 1243-1250 ◽  
Author(s):  
L. Rossetti ◽  
A. Giaccari ◽  
E. Klein-Robbenhaar ◽  
L. R. Vogel
Keyword(s):  
Trace Elements ◽  
Mode Of Action

Isolation of New Glycosides from Anemarrhena Asphodeloides Rhizome and Screening of their Anticancer Activity

2019 ◽  
Vol 16 (6) ◽  
pp. 474-477 ◽  
Author(s):  
Pham Van Khang ◽  
Nguyen Thi Hien Lan ◽  
Le Quang Truong ◽  
Mai Thi Minh Chau ◽  
Mai Xuan Truong ◽  
...  
Keyword(s):  
Anticancer Activity ◽  
Spectral Data ◽  
Cell Lines ◽  
Cancer Cell ◽  
Spectroscopic Analysis ◽  
2D Nmr ◽  
Ic50 Values ◽  
Nmr Techniques ◽  
Inhibitory Activities ◽  
Anemarrhena Asphodeloides

In this report, two new steroidal glycosides were isolated and determined from n-butanol fraction of A.asphodeloides. The structures were confirmed in comparison with the spectral data of known compounds by using different spectroscopic analysis approaches including 1D & 2D-NMR techniques and HRMS. The anti-proliferation screening against cancer cell lines A549 and HeLa indicated that compound 1 exhibited good inhibitory activities with IC50 values of 0.79 and 0.55 µg/mL, respectively.

Design, Synthesis and Biological Evaluation: 5-amino-1H-pyrazole-1- carbonyl derivatives as FGFR Inhibitors

2020 ◽  
Vol 17 (11) ◽  
pp. 1330-1341
Author(s):  
Yan Zhang ◽  
Niefang Yu
Keyword(s):  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cancer Cell Lines ◽  
Biological Evaluation ◽  
Human Gastric Cancer ◽  
Design Synthesis ◽  
Carbonyl Derivatives ◽  
Ic50 Values ◽  
Inhibitory Activities

Background: Fibroblast growth factors (FGFs) and their high affinity receptors (FGFRs) play a major role in cell proliferation, differentiation, migration, and apoptosis. Aberrant FGFR signaling pathway might accelerate development in a broad panel of malignant solid tumors. However, the full application of most existing small molecule FGFR inhibitors has become a challenge due to the potential target mutation. Hence, it has attracted a great deal of attention from both academic and industrial fields for hunting for novel FGFR inhibitors with potent inhibitory activities and high selectivity. Objective: Novel 5-amino-1H-pyrazole-1-carbonyl derivatives were designed, synthesized, and evaluated as FGFR inhibitors. Methods: A series of 5-amino-1H-pyrazole-1-carbonyl derivatives were established by a condensation of the suitable formyl acetonitrile derivatives with either hydrazine or hydrazide derivatives in the presence of anhydrous ethanol or toluene. The inhibitory activities of the target compounds were screened against the FGFRs and two representative cancer cell lines. Tests were carried out to observe the inhibition of 8e against FGFR phosphorylation and downstream signal phosphorylation in human gastric cancer cell lines (SNU-16). The molecular docking of all the compounds were performed using Molecular Operating Environment in order to evaluate their binding abilities with the corresponding protein kinase. Results: A series of 5-amino-1H-pyrazole-1-carbonyl derivatives have been designed and synthesized, screened for their inhibitory activities against FGFRs and cancer cell lines. Most of the target compounds showed moderate to good anti-proliferate activities against the tested enzymes and cell lines. The most promising compounds 8e suppressed FGFR1-3 with IC50 values of 56.4, 35.2, 95.5 nM, and potently inhibited the SNU-16 and MCF-7 cancer cells with IC50 values of 0.71 1.26 μM, respectively. And 8e inhibited the growth of cancer cells containing FGFR activated by multiple mechanisms. In addition, the binding interactions were quite similar in the molecular models between generated compounds and Debio-1347 with the FGFR1. Conclusion: According to the experimental findings, 5-amino-1H-pyrazole-1-carbonyl might serve as a promising template of an FGFR inhibitor.

scholarly journals Structural Characterization and Assessment of Anti-Inflammatory and Anti-Tyrosinase Activities of Polyphenols from Melastoma normale

Molecules ◽  
2021 ◽  
Vol 26 (13) ◽  
pp. 3913
Author(s):  
Rui-Jie He ◽  
Jun Li ◽  
Yong-Lin Huang ◽  
Ya-Feng Wang ◽  
Bing-Yuan Yang ◽  
...  
Keyword(s):  
Enzyme Inhibitors ◽  
Enzyme Inhibitor ◽  
Structure Identification ◽  
No Production ◽  
Protective Effects ◽  
Successful Isolation ◽  
Ic50 Values ◽  
Development And Utilization ◽  
Inhibitory Activities ◽  
Anti Inflammatory

Polyphenols, widely distributed in the genus Melastoma plants, possess extensive cellular protective effects such as anti-inflammatory, anti-tyrosinase, and anti-obesity, which makes it a potential anti-inflammatory drug or enzyme inhibitor. Therefore, the aim of this study is to screen for the anti-inflammatory and enzyme inhibitory activities of compounds from title plant. Using silica gel, MCI, ODS C18, and Sephadex LH-20 column chromatography, as well as semipreparative HPLC, the extract of Melastoma normale roots was separated. Four new ellagitannins, Whiskey tannin C (1), 1-O-(4-methoxygalloyl)-6-O-galloyl-2,3-O-(S)-hexahydroxydiphenoyl-β-d-glucose (2), 1-O-galloyl-6-O-(3-methoxygalloyl)-2,3-O-(S)-hexahydroxydiphenoyl-β-d-glucose (3), and 1-O-galloyl-6-O-vanilloyl-2,3-O-(S)-hexahydroxydiphenoyl-β-d-glucose (4), along with eight known polyphenols were firstly obtained from this plant. The structures of all isolates were elucidated by HRMS, NMR, and CD analyses. Using lipopolysaccharide (LPS)-stimulated RAW2 64.7 cells, we investigated the anti-inflammatory activities of compounds 1–4, unfortunately, none of them exhibit inhibit nitric oxide (NO) production, their IC50 values are all > 50 μM. Anti-tyrosinase activity assays was done by tyrosinase inhibition activity screening model. Compound 1 showed weak tyrosinase inhibitory activity with IC50 values of 426.02 ± 11.31 μM. Compounds 2–4 displayed moderate tyrosinase inhibitory activities with IC50 values in the range of 124.74 ± 3.12–241.41 ± 6.23 μM. The structure–activity relationships indicate that hydroxylation at C-3′, C-4′, and C-3 in the flavones were key to their anti-tyrosinase activities. The successful isolation and structure identification of ellagitannin provide materials for the screening of anti-inflammatory drugs and enzyme inhibitors, and also contribute to the development and utilization of M. normale.

scholarly journals Preparation and Characterization of the Sulfur-Impregnated Natural Zeolite Clinoptilolite for Hg(II) Removal from Aqueous Solutions

Processes ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 217
Author(s):  
Marin Ugrina ◽  
Martin Gaberšek ◽  
Aleksandra Daković ◽  
Ivona Nuić
Keyword(s):  
Chemical Modification ◽  
Aqueous Solutions ◽  
Specific Surface ◽  
Surface Area ◽  
Natural Zeolite ◽  
Contact Time ◽  
Liquid Ratio ◽  
X Ray ◽  
Solid Liquid

Sulfur-impregnated zeolite has been obtained from the natural zeolite clinoptilolite by chemical modification with Na2S at 150 °C. The purpose of zeolite impregnation was to enhance the sorption of Hg(II) from aqueous solutions. Chemical analysis, acid and basic properties determined by Bohem’s method, chemical behavior at different pHo values, zeta potential, cation-exchange capacity (CEC), specific surface area, X-ray powder diffraction (XRPD), scanning electron microscopy with energy-dispersive X-ray analysis (SEM-EDS), Fourier transform infrared spectroscopy (FTIR), as well as thermogravimetry with derivative thermogravimetry (TG-DTG) were used for detailed comparative mineralogical and physico-chemical characterization of natural and sulfur-impregnated zeolites. Results revealed that the surface of the natural zeolite was successfully impregnated with sulfur species in the form of FeS and CaS. Chemical modification caused an increase in basicity and the net negative surface charge due to an increase in oxygen-containing functional groups as well as a decrease in specific surface area and crystallinity due to the formation of sulfur-containing clusters at the zeolite surface. The sorption of Hg(II) species onto the sulfur-impregnated zeolite was affected by the pH, solid/liquid ratio, initial Hg(II) concentration, and contact time. The optimal sorption conditions were determined as pH 2, a solid/liquid ratio of 10 g/L, and a contact time of 800 min. The maximum obtained sorption capacity of the sulfur-impregnated zeolite toward Hg(II) was 1.02 mmol/g. The sorption mechanism of Hg(II) onto the sulfur-impregnated zeolite involves electrostatic attraction, ion exchange, and surface complexation, accompanied by co-precipitation of Hg(II) in the form of HgS. It was found that sulfur-impregnation enhanced the sorption of Hg(II) by 3.6 times compared to the natural zeolite. The leaching test indicated the retention of Hg(II) in the zeolite structure over a wide pH range, making this sulfur-impregnated sorbent a promising material for the remediation of a mercury-polluted environment.

scholarly journals New Diterpenoids and Isocoumarin Derivatives from the Mangrove-Derived Fungus Hypoxylon sp.

Marine Drugs ◽  
2021 ◽  
Vol 19 (7) ◽  
pp. 362
Author(s):  
Bolin Hou ◽  
Sushi Liu ◽  
Ruiyun Huo ◽  
Yueqian Li ◽  
Jinwei Ren ◽  
...  
Keyword(s):  
Nuclear Magnetic Resonance ◽  
Magnetic Resonance ◽  
Crude Extract ◽  
Mass Spectrometric ◽  
Spectrometric Analysis ◽  
Ic50 Values ◽  
Inhibitory Activities ◽  
The Absolute ◽  
Dpph Scavenging ◽  
New Compounds

Two new diterpenoids, hypoxyterpoids A (1) and B (2), and four new isocoumarin derivatives, hypoxymarins A–D (4–7), together, with seven known metabolites (3 and 8–13) were obtained from the crude extract of the mangrove-derived fungus Hypoxylon sp. The structures of the new compounds were elucidated on the basis of 1- and 2-dimensional (1D/2D) nuclear magnetic resonance (NMR) spectroscopic and mass spectrometric analysis. The absolute configurations of compounds 1, 2, 4, 5, and 7 were determined by comparison of experimental and calculated electronic circular dichroism (ECD) spectra, and the absolute configurations of C-4′ in 6 and C-9 in 7 were determined by [Rh2(OCOCF3)4]-induced ECD spectra. Compound 1 showed moderate α-glucosidase inhibitory activities with IC50 values of 741.5 ± 2.83 μM. Compounds 6 and 11 exhibited DPPH scavenging activities with IC50 values of 15.36 ± 0.24 and 3.69 ± 0.07 μM, respectively.

Sign in / Sign up

Export Citation Format

Share Document