Highly potent inhibition of tyrosinase by mulberrosides and the inhibitory mechanism in vitro

2021 ◽  
Author(s):  
Xiang Liu ◽  
Jinqiu Rao ◽  
Kai Wang ◽  
Meijun Wang ◽  
Tie Yao ◽  
...  
Keyword(s):  
Inhibitory Mechanism ◽  
Potent Inhibition

Novel Iodinated Hydrazide-hydrazones and their Analogues as Acetyl- and Butyrylcholinesterase Inhibitors

2020 ◽  
Vol 20 (23) ◽  
pp. 2106-2117
Author(s):  
Martin Krátký ◽  
Šárka Štěpánková ◽  
Michaela Brablíková ◽  
Katarína Svrčková ◽  
Markéta Švarcová ◽  
...  
Keyword(s):  
Biological Activities ◽  
Structural Parameters ◽  
Covalent Binding ◽  
Docking Studies ◽  
Potent Inhibition ◽  
Brain Barrier Permeability ◽  
Electric Eel ◽  
Ic50 Values ◽  
Ellman’S Method

Background: Hydrazide-hydrazones have been known as scaffold with various biological activities including inhibition of acetyl- (AChE) and butyrylcholinesterase (BuChE). Cholinesterase inhibitors are mainstays of dementias’ treatment. Objective: Twenty-five iodinated hydrazide-hydrazones and their analogues were designed as potential central AChE and BuChE inhibitors. Methods: Hydrazide-hydrazones were synthesized from 4-substituted benzohydrazides and 2-/4- hydroxy-3,5-diiodobenzaldehydes. The compounds were investigated in vitro for their potency to inhibit AChE from electric eel and BuChE from equine serum using Ellman’s method. We calculated also physicochemical and structural parameters for CNS delivery. Results: The derivatives exhibited a moderate dual inhibition with IC50 values ranging from 15.1-140.5 and 35.5 to 170.5 μmol.L-1 for AChE and BuChE, respectively. Generally, the compounds produced a balanced or more potent inhibition of AChE. N'-[(E)-(4-Hydroxy-3,5-diiodophenyl)methylidene]-4- nitrobenzohydrazide 2k and 4-fluoro-N'-(2-hydroxy-3,5-diiodobenzyl)benzohydrazide 3a were the most potent inhibitors of AChE and BuChE, respectively. Structure-activity relationships were established, and molecular docking studies confirmed interaction with enzymes. Conclusion: Many novel hydrazide-hydrazones showed lower IC50 values than rivastigmine against AChE and some of them were comparable for BuChE to this drug used for the treatment of dementia. They interact with cholinesterases via non-covalent binding into the active site. Based on the BOILEDEgg approach, the majority of the derivatives met the criteria for blood-brain-barrier permeability.

scholarly journals Characterization of LDD-2633 as a Novel RET Kinase Inhibitor with Anti-Tumor Effects in Thyroid Cancer

2021 ◽  
Vol 14 (1) ◽  
pp. 38
Author(s):  
Hyo Jeong Lee ◽  
Pyeonghwa Jeong ◽  
Yeongyu Moon ◽  
Jungil Choi ◽  
Jeong Doo Heo ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Thyroid Carcinoma ◽  
Kinase Inhibitor ◽  
Point Mutations ◽  
Carcinoma Cells ◽  
Medullary Thyroid ◽  
Potent Inhibition ◽  
Kinase Inhibitory Activity

Rearranged during transfection (RET), a receptor tyrosine kinase, is activated by glial cell line-derived neurotrophic factor family ligands. Chromosomal rearrangement or point mutations in RET are observed in patients with papillary thyroid and medullary thyroid carcinomas. Oncogenic alteration of RET results in constitutive activation of RET activity. Therefore, inhibiting RET activity has become a target in thyroid cancer therapy. Here, the anti-tumor activity of a novel RET inhibitor was characterized in medullary thyroid carcinoma cells. The indirubin derivative LDD-2633 was tested for RET kinase inhibitory activity. In vitro, LDD-2633 showed potent inhibition of RET kinase activity, with an IC50 of 4.42 nM. The growth of TT thyroid carcinoma cells harboring an RET mutation was suppressed by LDD-2633 treatment via the proliferation suppression and the induction of apoptosis. The effects of LDD-2633 on the RET signaling pathway were examined; LDD-2633 inhibited the phosphorylation of the RET protein and the downstream molecules Shc and ERK1/2. Oral administration of 20 or 40 mg/kg of LDD-2633 induced dose-dependent suppression of TT cell xenograft tumor growth. The in vivo and in vitro experimental results supported the potential use of LDD-2633 as an anticancer drug for thyroid cancers.

scholarly journals Curcumin-removed turmeric oleoresin nano-emulsion as a novel botanical fungicide to control anthracnose (Colletotrichum gloeosporioides) in litchi

2021 ◽  
Vol 10 (1) ◽  
pp. 729-741
Author(s):  
Van Cuong Bui ◽  
The Tam Le ◽  
Tuyen Hong Nguyen ◽  
Nam Thi Pham ◽  
Hoang Dinh Vu ◽  
...  
Keyword(s):  
Field Trial ◽  
Colletotrichum Gloeosporioides ◽  
Inhibitory Concentration ◽  
Particle Sizes ◽  
Control Efficacy ◽  
Potent Inhibition ◽  
Nano Emulsion ◽  
Nano Formulation

Abstract During curcumin production in Vietnam, curcumin-removed turmeric oleoresin (CRTO) has been considered as a by-product. It costs to treat the by-product to prevent environmental pollution. In this study, the by-product was utilized as an active ingredient for preparing a botanical fungicide-based nano-emulsion and evaluated for its in vitro and in vivo control efficacy against Colletotrichum gloeosporioides, a causal agent of anthracnose of litchi, in the laboratory as well as a field trial. The nano-emulsion is colloidally stable and uniform with particle sizes of 95–250 nm. CRTO nano-emulsion significantly affected various Colletotrichum species. Notably, this nano-emulsion showed potent inhibition for the mycelial growth of C. gloeosporioides and solidly suppressed the development of anthracnose on litchi fruits. In the in vitro inhibition test, the equivalent half-maximal inhibitory concentration of CRTO in nano-formulation was 0.11 mg·mL−1, which was 3.0× and 6.1× lower than IC50 values of CRTO alone (0.33 mg·mL−1) and a mixture of curcuminoids (0.48 mg·mL−1), respectively. In the field trial, the litchi anthracnose infection was effectively controlled by nano-formulation. These results suggest that CRTO nano-emulsion could be used as an alternative to harmful synthetic fungicides to control anthracnose on litchi fruits.

scholarly journals Synthesis, Characterization and Evaluation of Anti-inflammatory Activity of Novel Indoline Derivatives

2016 ◽  
Vol 12 (12) ◽  
pp. 4557-4563
Author(s):  
Dhinesh kumar Manoharan
Keyword(s):  
1H Nmr ◽  
13C Nmr ◽  
Protein Denaturation ◽  
Inflammatory Activity ◽  
Potent Inhibition ◽  
Ft Ir ◽  
Anti Inflammatory

Series of indoline derivatives were synthesized using N-(4-aminophenyl) indoline-1-carbothiamide as a precursor. The structures of synthesized compounds were confirmed by   FT-IR, 1H-NMR, 13C-NMR and LC-MS. The in vitro anti-inflammatory activity of synthesized indoline derivatives were examined by standard anti-denaturation assay. The compounds 4a (IC50 = 62.2 µg/ml) and 4b (IC50 = 60.7 µg/ml) showed potent inhibition on protein denaturation. The compounds 5a (IC50 = 97.8 µg/ml) exhibits moderate inhibition on protein denaturation

scholarly journals In VitroAntibacterial Activity of the Ceftazidime-Avibactam (NXL104) Combination against Pseudomonas aeruginosa Clinical Isolates

2012 ◽  
Vol 56 (3) ◽  
pp. 1606-1608 ◽  
Author(s):  
Premavathy Levasseur ◽  
Anne-Marie Girard ◽  
Monique Claudon ◽  
Herman Goossens ◽  
Michael T. Black ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Antibacterial Activity ◽  
Content Type ◽  
Reference Treatment ◽  
Common Reference ◽  
Class A ◽  
Potent Inhibition ◽  
Efficient Protection ◽  
Lactamase Inhibitor

ABSTRACTThe β-lactamase inhibitor avibactam (NXL104) displays potent inhibition of both class A and C enzymes. Thein vitroantibacterial activity of the combination ceftazidime-avibactam was evaluated against a clinical panel ofPseudomonas aeruginosaisolates. Avibactam offered efficient protection from hydrolysis since 94% of isolates were susceptible to ceftazidime when combined with 4 μg/ml avibactam, compared with 65% susceptible to ceftazidime alone. Ceftazidime-avibactam also demonstrated better antipseudomonal activity than imipenem (82% susceptibility), a common reference treatment.

scholarly journals Mesyl phosphoramidate backbone modified antisense oligonucleotides targeting miR-21 with enhanced in vivo therapeutic potency

2020 ◽  
Vol 117 (51) ◽  
pp. 32370-32379
Author(s):  
Olga A. Patutina ◽  
Svetlana K. Gaponova (Miroshnichenko) ◽  
Aleksandra V. Sen’kova ◽  
Innokenty A. Savin ◽  
Daniil V. Gladkikh ◽  
...  
Keyword(s):  
Tumor Model ◽  
Rnase H ◽  
Mouse Tumor ◽  
Internal Organs ◽  
Potent Inhibition ◽  
Nuclease Resistance ◽  
New Type

The design of modified oligonucleotides that combine in one molecule several therapeutically beneficial properties still poses a major challenge. Recently a new type of modified mesyl phosphoramidate (or µ-) oligonucleotide was described that demonstrates high affinity to RNA, exceptional nuclease resistance, efficient recruitment of RNase H, and potent inhibition of key carcinogenesis processes in vitro. Herein, using a xenograft mouse tumor model, it was demonstrated that microRNA miR-21–targeted µ-oligonucleotides administered in complex with folate-containing liposomes dramatically inhibit primary tumor growth via long-term down-regulation of miR-21 in tumors and increase in biosynthesis of miR-21–regulated tumor suppressor proteins. This antitumoral effect is superior to the effect of the corresponding phosphorothioate. Peritumoral administration of µ-oligonucleotide results in its rapid distribution and efficient accumulation in the tumor. Blood biochemistry and morphometric studies of internal organs revealed no pronounced toxicity of µ-oligonucleotides. This new oligonucleotide class provides a powerful tool for antisense technology.

scholarly journals Molecular Insight into the Anti-Inflammatory Effects of the Curcumin Ester Prodrug Curcumin Diglutaric Acid In Vitro and In Vivo

2020 ◽  
Vol 21 (16) ◽  
pp. 5700 ◽  
Author(s):  
Rianthong Phumsuay ◽  
Chawanphat Muangnoi ◽  
Peththa Wadu Dasuni Wasana ◽  
Hasriadi Hasriadi ◽  
Opa Vajragupta ◽  
...  
Keyword(s):  
Time Course ◽  
Area Under The Curve ◽  
Dependent Manner ◽  
Paw Edema ◽  
Inflammatory Agent ◽  
Potent Inhibition ◽  
Anti Inflammatory ◽  
Ester Prodrug

Curcumin diglutaric acid (CurDG), an ester prodrug of curcumin, has the potential to be developed as an anti-inflammatory agent due to its improved solubility and stability. In this study, the anti-inflammatory effects of CurDG were evaluated. The effects of CurDG on inflammatory mediators were evaluated in LPS-stimulated RAW 264.7 macrophage cells. CurDG reduced the increased levels of NO, IL-6, and TNF- α, as well as iNOS and COX-2 expression in cells to a greater extent than those of curcumin, along with the potent inhibition of MAPK (ERK1/2, JNK, and p38) activity. The anti-inflammatory effects were assessed in vivo by employing a carrageenan-induced mouse paw edema model. Oral administration of CurDG demonstrated significant anti-inflammatory effects in a dose-dependent manner in mice. The effects were significantly higher compared to those of curcumin at the corresponding doses (p < 0.05). Moreover, 25 mg/kg curcumin did not exert a significant anti-inflammatory effect for the overall time course as indicated by the area under the curve data, while the equimolar dose of CurDG produced significant anti-inflammatory effects comparable with 50, 100, and 200 mg/kg curcumin (p < 0.05). Similarly, CurDG significantly reduced the proinflammatory cytokine expression in paw edema tissues compared to curcumin (p < 0.05). These results provide the first experimental evidence for CurDG as a promising anti-inflammatory agent.

siRNA Versus Antisense Locked Nucleic Acids: Stay Single!.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 614-614
Author(s):  
Phil Kearney ◽  
Majken Westergaard ◽  
Henrik F. Hansen ◽  
Ellen M. Staarup ◽  
Troels Koch ◽  
...  
Keyword(s):  
Nucleic Acid ◽  
Therapeutic Option ◽  
Phase 1 ◽  
Locked Nucleic Acid ◽  
Target Validation ◽  
Host Animal ◽  
Clinical Phase ◽  
Potent Inhibition

Abstract Much discussion has centred around the utility and benefits of siRNA in both target validation and as a therapeutic option. This has been driven by significant publications including that of Soutcheck et al (Nature432, 173–177 2004), which demonstrated liver targeting as well as in vivo efficacy when siRNA against ApoB was tethered to a cholesterol moiety. Santaris Pharma has developed a third generation nucleic acid chemistry referred to as locked nucleic acid (LNA) which delivers unmatched affinity and stabiliy benefits, largely overcoming the drawbacks associated with traditional antisense molecules. We therefore sought to compare this chemistry with targets which siRNA has been successfully used in in vivo/in vitro settings. The same motif used in the Soutcheck study was targeted with a LNA molecule, and the free siRNA activity was compared to the cholesterol linked and free LNA molecules in their ability ot down regulate ApoB expression. LNA (SPC3197) inhibited ApoB expression by 90% while at an equimolar concentration siRNA was ineffective in the liver and jejunum. Cholesterol linked siRNA was only effective in the jejunum (c50% reduction in mRNA) Fig1. Only the LNA mediated inhibition of ApoB expression was paralleled by a drop in serum cholesterol in the host animal. In a second model siRNA molecules targeting Hif-1a mRNA (Yu et al Lab Invest84, 553–561 2004) were compared to our lead LNA molecule targeting Hif-1a, SPC2968. Interestingly in in vitro analyses these 2 molecules were equally effective. However in a murine model the increased half life of the LNA molecules translated to a potent inhibition of Hif-1a as measured by QPCR. This effect was noted in jejunum and liver, and persisted for at least 4 days. Hif-1a inhibition mediated by siRNA was not seen in any tissue analysed (Fig 2). Finally a 3rd molecule targeting Bcl-2 has entered clinical Phase 1 trials, and data will be presented documenting its improved affinity and stabitily in relation to competitor molecules such as Genasense. Figure Figure

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