scholarly journals Inhibitory Effect of Chlorogenic Acid Analogues Comprising Pyridine and Pyrimidine on α-MSH-Stimulated Melanogenesis and Stability of Acyl Analogues in Methanol

2021 ◽  
Vol 14 (11) ◽  
pp. 1176
Author(s):  
Jaeuk Sim ◽  
Srinu Lanka ◽  
Jeong-Woong Jo ◽  
Chhabi Lal Chaudhary ◽  
Manjunatha Vishwanath ◽  
...  
Keyword(s):  
Chlorogenic Acid ◽  
Kojic Acid ◽  
Inhibitory Effect ◽  
B16 Melanoma ◽  
Design Synthesis ◽  
Meta Position ◽  
Sar Studies ◽  
Key Factor ◽  
The Stability ◽  
Positive Controls

In continuation of studies for α-MSH stimulated melanogenesis inhibitors, we have evaluated the design, synthesis, and activity of a new series of chlorogenic acid (CGA) analogues comprising pyridine, pyrimidine, and diacyl derivatives. Among nineteen synthesized compounds, most of them (fifteen) exhibited better inhibitions of melanin formation in B16 melanoma cells. The results illustrated that a pyridine analogue 6f and a diacyl derivative 13a of CGA showed superior inhibition profiles (IC50: 2.5 ± 0.7 μM and 1.1 ± 0.1 μM, respectively) of α-MSH activities than positive controls, kojic acid and arbutin (IC50: 54 ± 1.5 μM and 380 ± 9.5 μM, respectively). The SAR studies showed that both –CF3 and –Cl groups exhibited better inhibition at the meta position on benzylamine than their ortho and para positions. In addition, the stability of diacyl analogues of CGA in methanol monitored by HPLC for 28 days indicated the steric bulkiness of acyl substituents as a key factor in their stability.

Development of Novel Glitazones as Antidiabetic Agents: Molecular Design, Synthesis, Evaluation of Glucose Uptake Activity and SAR Studies

2020 ◽  
Vol 17 (7) ◽  
pp. 840-849
Author(s):  
Mahendra Gowdru Srinivas ◽  
Prabitha Prabhakaran ◽  
Subhankar Probhat Mandal ◽  
Yuvaraj Sivamani ◽  
Pranesh Guddur ◽  
...  
Keyword(s):  
Glucose Uptake ◽  
Molecular Design ◽  
Docking Studies ◽  
Antidiabetic Activity ◽  
Design Synthesis ◽  
In Silico Docking ◽  
Ppar Γ ◽  
Sar Studies ◽  
Structure Activity ◽  
Uptake Activity

Background: Thiazolidinediones and its bioisostere, namely, rhodanines have become ubiquitous class of heterocyclic compounds in drug design and discovery. In the present study, as part of molecular design, a series of novel glitazones that are feasible to synthesize in our laboratory were subjected to docking studies against PPAR-γ receptor for their selection. Methods and Results: As part of the synthesis of selected twelve glitazones, the core moiety, pyridine incorporated rhodanine was synthesized via dithiocarbamate. Later, a series of glitazones were prepared via Knovenageal condensation. In silico docking studies were performed against PPARγ protein (2PRG). The titled compounds were investigated for their cytotoxic activity against 3T3-L1 cells to identify the cytotoxicity window of the glitazones. Further, within the cytotoxicity window, glitazones were screened for glucose uptake activity against L6 cells to assess their possible antidiabetic activity. Conclusion: Based on the glucose uptake results, structure activity relationships are drawn for the title compounds.

scholarly journals The influence of sugar–protein complexes on the thermostability of C-reactive protein (CRP)

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Andreea Lorena Mateescu ◽  
Nicolae-Bogdan Mincu ◽  
Silvana Vasilca ◽  
Roxana Apetrei ◽  
Diana Stan ◽  
...  
Keyword(s):  
Diagnostic Tests ◽  
Protein Complexes ◽  
C Reactive Protein ◽  
Time Resolved Fluorescence ◽  
Time Resolved ◽  
Reactive Protein ◽  
In Vitro Diagnostic ◽  
The Stability ◽  
Positive Controls

AbstractThe purpose of the present study was to evaluate de influence of protein–sugar complexation on the stability and functionality of C-reactive protein, after exposure to constant high temperatures, in order to develop highly stable positive controls for in-vitro diagnostic tests. C-reactive protein is a plasmatic protein used as a biomarker for the diagnosis of a series of health problems such as ulcerative colitis, cardiovascular diseases, metabolic syndrome, due to its essential role in the evolution of chronic inflammation. The sugar–protein interaction was investigated using steady state and time resolved fluorescence. The results revealed that there are more than two classes of tryptophan, with different degree of accessibility for the quencher molecule. Our study also revealed that sugar–protein complexes have superior thermostability, especially after gamma irradiation at 2 kGy, the protein being stable and functional even after 22 days exposure to 40 °C.

scholarly journals Sulfaguanidine Hybrid with Some New Pyridine-2-One Derivatives: Design, Synthesis, and Antimicrobial Activity against Multidrug-Resistant Bacteria as Dual DNA Gyrase and DHFR Inhibitors

Antibiotics ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 162
Author(s):  
Ahmed Ragab ◽  
Sawsan A. Fouad ◽  
Ola A. Abu Ali ◽  
Entsar M. Ahmed ◽  
Abeer M. Ali ◽  
...  
Keyword(s):  
Antimicrobial Activity ◽  
Fungal Growth ◽  
Dna Gyrase ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Design Synthesis ◽  
Potent Inhibition ◽  
Ic50 Values ◽  
Dhfr Inhibitors ◽  
Positive Controls

Herein, a series of novel hybrid sulfaguanidine moieties, bearing 2-cyanoacrylamide 2a–d, pyridine-2-one 3–10, and 2-imino-2H-chromene-3-carboxamide 11, 12 derivatives, were synthesized, and their structure confirmed by spectral data and elemental analysis. All the synthesized compounds showed moderate to good antimicrobial activity against eight pathogens. The most promising six derivatives, 2a, 2b, 2d, 3a, 8, and 11, revealed to be best in inhibiting bacterial and fungal growth, thus showing bactericidal and fungicidal activity. These derivatives exhibited moderate to potent inhibition against DNA gyrase and DHFR enzymes, with three derivatives 2d, 3a, and 2a demonstrating inhibition of DNA gyrase, with IC50 values of 18.17–23.87 µM, and of DHFR, with IC50 values of 4.33–5.54 µM; their potency is near to that of the positive controls. Further, the six derivatives exhibited immunomodulatory potential and three derivatives, 2d, 8, and 11, were selected for further study and displayed an increase in spleen and thymus weight and enhanced the activation of CD4+ and CD8+ T lymphocytes. Finally, molecular docking and some AMED studies were performed.

scholarly journals Development of a High-Throughput Method to Study the Inhibitory Effect of Phytochemicals on Trimethylamine Formation

Nutrients ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1466
Author(s):  
Lisard Iglesias-Carres ◽  
Lauren A. Essenmacher ◽  
Kathryn C. Racine ◽  
Andrew P. Neilson
Keyword(s):  
Chlorogenic Acid ◽  
Gallic Acid ◽  
High Throughput ◽  
Anaerobic Fermentation ◽  
Inhibitory Effect ◽  
Healthy Human ◽  
High Throughput Method ◽  
Lyase Activity ◽  
Inhibitory Potential ◽  
Potential Maximum

Choline is metabolized by the gut microbiota into trimethylamine (TMA), the precursor of pro-atherosclerotic molecule trimethylamine N-oxide (TMAO). A reduction in TMA formation has shown cardioprotective effects, and some phytochemicals may reduce TMA formation. This study aimed to develop an optimized, high-throughput anaerobic fermentation methodology to study the inhibition of choline microbial metabolism into TMA by phenolic compounds with healthy human fecal starter. Optimal fermentation conditions were: 20% fecal slurry (1:10 in PBS), 100 µM choline, and 12 h fermentation. Additionally, 10 mM of 3,3-dimethyl-1-butanol (DMB) was defined as a positive TMA production inhibitor, achieving a ~50% reduction in TMA production. Gallic acid and chlorogenic acid reported higher TMA inhibitory potential (maximum of 80–90% TMA production inhibition), with IC50 around 5 mM. Neither DMB nor gallic acid or chlorogenic acid reduced TMA production through cytotoxic effects, indicating mechanisms such as altered TMA-lyase activity or expression.

scholarly journals Anti-diabetes Constituents in Leaves of Smallanthus sonchifolius

2010 ◽  
Vol 5 (1) ◽  
pp. 1934578X1000500 ◽  
Author(s):  
Xiang Zheng ◽  
He Fan ◽  
Kang Ting-Guo ◽  
Dou De-Qiang ◽  
Gai Kuo ◽  
...  
Keyword(s):  
Quality Control ◽  
Chlorogenic Acid ◽  
Caffeic Acid ◽  
Analytical Method ◽  
Inhibitory Effect ◽  
Hplc Method ◽  
Smallanthus Sonchifolius ◽  
Rp Hplc

The inhibitory effect of smallanthaditerpenic acids A, B, C and D previously isolated from leaves of Smallanthus sonchifolius (yacon) on α-glucosidase were examined and their IC50 were determined to be 0.48 mg/mL, 0.59 mg/mL, 1.00 mg/mL, and 1.17 mg/mL respectively. In addition, a rapid, reliable RP-HPLC method for the analysis of chlorogenic acid, caffeic acid, and smallanthaditerpenic acids A and C in yacon leaves was established, and the variation in their contents in leaves from plants cultivated in different places and collected at different times of the year were compared. The established analytical method for determining smallanthaditerpenic acids A and C, chlorogenic acid and caffeic acid presented good results and could be used as a method for the quality control of S. sonchifolius leaves.

Release Profile of a Model Protein Drug Depending on the Stability of Microspheres Based on Polyelectrolyte Complex

2007 ◽  
Vol 342-343 ◽  
pp. 505-508
Author(s):  
Sung Won Kim ◽  
Yun Sik Nam ◽  
Yeon Jin Min ◽  
Jong Ho Kim ◽  
Kwang Meyong Kim ◽  
...  
Keyword(s):  
Polyelectrolyte Complex ◽  
Coating Layer ◽  
Great Influence ◽  
Release Profile ◽  
Core Material ◽  
Glycol Chitosan ◽  
The Core ◽  
Key Factor ◽  
Model Protein ◽  
The Stability

Stability and disintegration of natural polyelectrolyte complex microspheres for protein drugs delivery have been extensively investigated because of their great influence on the drug release patterns. In this study, we tested stability of microspheres with alginate (Alg) core layered by either chitosan (Chi) or glycol chitosan (GChi) by examining release profiles of fluorophorelabeled bovine serum albumin (BSA) and lysozyme (Lys) from the microspheres. While GChi shell was disintegrated quickly, Chi-shell microspheres showed good stability in PBS. Disintegration of the coated layer induced the core material instable. The results indicated that while the charges of the shell material provided additional diffusion barrier against the protein release, the key factor to hold the proteins inside the microspheres was the integrity of the outer coating layer.

scholarly journals Sorption and Desorption Analysis of Nitrobenzene on Differently Functionalized Multiwalled Carbon Nanotubes and Implications on the Stability

Water ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 1426
Author(s):  
Zhanhua Ji ◽  
Dengyu Li
Keyword(s):  
Carbon Nanotubes ◽  
Underlying Mechanism ◽  
Multiwalled Carbon ◽  
Environmental Behaviors ◽  
Initial Concentration ◽  
Sorption Hysteresis ◽  
Key Factor ◽  
Functionalized Multiwalled Carbon Nanotubes ◽  
The Stability ◽  
Adsorption Desorption

The stability of carbon nanotubes (CNTs) suspension is a key factor in determining their transport, fate, and toxicity in an aquatic environment, which is significantly influenced by CNTs’ nature and water chemistry. Macromolecular dissolved organic matter (DOM) is reported to influence the stability of CNTs aggregation. However, little is known on small polar dissolved organic compound’s effects on CNTs aggregation. Nitrobenzene was selected to investigate its interaction with three different functionalized multiwalled CNTs (MWCNTs). Both the stability of CNTs aggregation and sorption hysteresis were affected by the initial concentration of nitrobenzene and the surface functionalization coverage of MWCNTs. At the initial concentration below 580 mg/L, the thermodynamic index of irreversibility (TII) and turbidity of CNTs suspension had the same tendency, indicating that the underlying mechanism is closely related. A conceptual adsorption–desorption model was proposed to further explain the relationship between the sorption hysteresis and stability of MWCNTs suspension under different initial concentrations of nitrobenzene. This provided data support to further clarify the environmental behaviors and risks of CNTs.

scholarly journals Cyclic GMP regulates activation of phosphoinositidase C by bradykinin in sensory neurons

1996 ◽  
Vol 316 (2) ◽  
pp. 539-544 ◽  
Author(s):  
Justine S. HARVEY ◽  
Gillian M. BURGESS
Keyword(s):  
Cyclic Gmp ◽  
Inhibitory Effect ◽  
Neonatal Rat ◽  
Drg Neurons ◽  
Rapid Phase ◽  
Surface Receptors ◽  
Similar Inhibitory Effect ◽  
Key Factor ◽  
The Right ◽  
Oxide Synthase

Prior exposure of cultured neonatal rat dorsal root ganglion (DRG) neurons to bradykinin resulted in marked attenuation of bradykinin-induced activation of phosphoinositidase C (PIC). The (logconcentration)–response curve for bradykinin-induced [3H]inositol trisphosphate ([3H]IP3) formation was shifted to the right and the maximum response was reduced. Bradykinin increases cyclic GMP (cGMP) in DRG neurons [Burgess, Mullaney, McNeill, Coote, Minhas and Wood (1989) J. Neurochem. 53, 1212–1218] and treatment of the neurons with dibutyryl cGMP (dbcGMP) had a similar, inhibitory, effect on bradykinin-induced [3H]IP3 formation. NG-Nitro-L-arginine (LNNA) blocked bradykinin-induced formation of cGMP. It prevented the functional uncoupling induced by pretreatment with bradykinin, but not the inhibitory effect of dbcGMP on [3H]IP3 formation. The ability of LNNA to prevent desensitization was reversed by excess L-arginine, indicating that its actions were mediated through inhibition of nitric oxide synthase. In addition to functional desensitization, exposure to bradykinin reduced the number of cell-surface receptors detected with [3H]bradykinin, without affecting its KD value for the remaining sites. In contrast to bradykinin, pretreatment with dbcGMP had no effect on either the KD or Bmax for [3H]bradykinin binding. This implies that the inhibitory effect of dbcGMP was downstream from the binding of bradykinin to its receptor and upstream of IP3 formation. The lack of effect of dbcGMP on [3H]bradykinin binding suggests that the decrease in receptor number induced by bradykinin was mediated by a different mechanism and was not a key factor in the rapid phase of desensitization in these cells.

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