Design and Synthesis of the First Generation of Novel Potent, Selective, and in Vivo Active (Benzothiazol-2-yl)acetonitrile Inhibitors of the c-Jun N-Terminal Kinase

2005 ◽  
Vol 48 (14) ◽  
pp. 4596-4607 ◽  
Author(s):  
Pascale Gaillard ◽  
Isabelle Jeanclaude-Etter ◽  
Vittoria Ardissone ◽  
Steve Arkinstall ◽  
Yves Cambet ◽  
...  
Keyword(s):  
First Generation ◽  
Design And Synthesis

THE ROLE OF POLYETHYLENIMINE IN ENHANCING PERFORMANCE OF GLUTAMATE BIOSENSORS

2018 ◽  
Vol 8 (3) ◽  
pp. 36-41
Author(s):  
Diep Do Thi Hong ◽  
Duong Le Phuoc ◽  
Hoai Nguyen Thi ◽  
Serra Pier Andrea ◽  
Rocchitta Gaia
Keyword(s):  
First Generation ◽  
Good Reproducibility ◽  
Complex Matrices ◽  
Long Term Stability ◽  
In Vitro Characterization ◽  
Glutamate Oxidase

Background: The first biosensor was constructed more than fifty years ago. It was composed of the biorecognition element and transducer. The first-generation enzyme biosensors play important role in monitoring neurotransmitter and determine small quantities of substances in complex matrices of the samples Glutamate is important biochemicals involved in energetic metabolism and neurotransmission. Therefore, biosensors requires the development a new approach exhibiting high sensibility, good reproducibility and longterm stability. The first-generation enzyme biosensors play important role in monitoring neurotransmitter and determine small quantities of substances in complex matrices of the samples. The aims of this work: To find out which concentration of polyethylenimine (PEI) exhibiting the most high sensibility, good reproducibility and long-term stability. Methods: We designed and developed glutamate biosensor using different concentration of PEI ranging from 0% to 5% at Day 1 and Day 8. Results: After Glutamate biosensors in-vitro characterization, several PEI concentrations, ranging from 0.5% to 1% seem to be the best in terms of VMAX, the KM; while PEI content ranging from 0.5% to 1% resulted stable, PEI 1% displayed an excellent stability. Conclusions: In the result, PEI 1% perfomed high sensibility, good stability and blocking interference. Furthermore, we expect to develop and characterize an implantable biosensor capable of detecting glutamate, glucose in vivo. Key words: Glutamate biosensors, PEi (Polyethylenimine) enhances glutamate oxidase, glutamate oxidase biosensors

scholarly journals A small molecule HIF-1α stabilizer that accelerates diabetic wound healing

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Guodong Li ◽  
Chung-Nga Ko ◽  
Dan Li ◽  
Chao Yang ◽  
Wanhe Wang ◽  
...  
Keyword(s):  
Wound Healing ◽  
Small Molecule ◽  
Hypoxia Inducible Factor ◽  
Diabetic Patients ◽  
Diabetic Mice ◽  
Impaired Wound Healing ◽  
Von Hippel Lindau ◽  
Design And Synthesis

AbstractImpaired wound healing and ulcer complications are a leading cause of death in diabetic patients. In this study, we report the design and synthesis of a cyclometalated iridium(III) metal complex 1a as a stabilizer of hypoxia-inducible factor-1α (HIF-1α). In vitro biophysical and cellular analyses demonstrate that this compound binds to Von Hippel-Lindau (VHL) and inhibits the VHL–HIF-1α interaction. Furthermore, the compound accumulates HIF-1α levels in cellulo and activates HIF-1α mediated gene expression, including VEGF, GLUT1, and EPO. In in vivo mouse models, the compound significantly accelerates wound closure in both normal and diabetic mice, with a greater effect being observed in the diabetic group. We also demonstrate that HIF-1α driven genes related to wound healing (i.e. HSP-90, VEGFR-1, SDF-1, SCF, and Tie-2) are increased in the wound tissue of 1a-treated diabetic mice (including, db/db, HFD/STZ and STZ models). Our study demonstrates a small molecule stabilizer of HIF-1α as a promising therapeutic agent for wound healing, and, more importantly, validates the feasibility of treating diabetic wounds by blocking the VHL and HIF-1α interaction.

scholarly journals Recent Advancements in Polymer/Liposome Assembly for Drug Delivery: From Surface Modifications to Hybrid Vesicles

Polymers ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1027
Author(s):  
Vincenzo De Leo ◽  
Francesco Milano ◽  
Angela Agostiano ◽  
Lucia Catucci
Keyword(s):  
Drug Delivery ◽  
First Generation ◽  
Phospholipid Bilayer ◽  
Bioactive Molecules ◽  
Systemic Delivery ◽  
Molecular Weights ◽  
Liposome Preparation ◽  
Wide Range ◽  
Liposome Surface

Liposomes are consolidated and attractive biomimetic nanocarriers widely used in the field of drug delivery. The structural versatility of liposomes has been exploited for the development of various carriers for the topical or systemic delivery of drugs and bioactive molecules, with the possibility of increasing their bioavailability and stability, and modulating and directing their release, while limiting the side effects at the same time. Nevertheless, first-generation vesicles suffer from some limitations including physical instability, short in vivo circulation lifetime, reduced payload, uncontrolled release properties, and low targeting abilities. Therefore, liposome preparation technology soon took advantage of the possibility of improving vesicle performance using both natural and synthetic polymers. Polymers can easily be synthesized in a controlled manner over a wide range of molecular weights and in a low dispersity range. Their properties are widely tunable and therefore allow the low chemical versatility typical of lipids to be overcome. Moreover, depending on their structure, polymers can be used to create a simple covering on the liposome surface or to intercalate in the phospholipid bilayer to give rise to real hybrid structures. This review illustrates the main strategies implemented in the field of polymer/liposome assembly for drug delivery, with a look at the most recent publications without neglecting basic concepts for a simple and complete understanding by the reader.

Design and synthesis of a potent and specific renin inhibitor with a prolonged duration of action in vivo

1986 ◽  
Vol 29 (10) ◽  
pp. 2088-2093 ◽  
Author(s):  
Suvit Thaisrivongs ◽  
Donald T. Pals ◽  
Douglas W. Harris ◽  
Warren M. Kati ◽  
Steve R. Turner
Keyword(s):  
Renin Inhibitor ◽  
Duration Of Action ◽  
Design And Synthesis ◽  
Prolonged Duration

scholarly journals Design and Synthesis of Pyrazole-3-one Derivatives as Hypoglycaemic Agents

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Prasanna A. Datar ◽  
Sonali R. Jadhav
Keyword(s):  
Amino Acid ◽  
Docking Studies ◽  
Diabetic Rats ◽  
Hypoglycemic Activity ◽  
Amino Acid Residues ◽  
Docking Score ◽  
Design And Synthesis ◽  
Hypoglycaemic Agents ◽  
Standard Compound

Pyrazole-3-one compounds were designed on the basis of docking studies of previously reported antidiabetic pyrazole compounds. The amino acid residues found during docking studies were used as guidelines for the modification of aromatic substitutions on pyrazole-3-one structure. Depending on the docking score, the designed compounds were selectively prioritized for synthesis. The synthesized compounds were subjected to in vivo hypoglycemic activity using alloxan induced diabetic rats and metformin as a standard. Compound 4 having sulphonamide derivative was found to be the most potent compound among the series.

scholarly journals Structure Based Design and Synthesis of Peptide Inhibitor of Human LOX-12: In Vitro and In Vivo Analysis of a Novel Therapeutic Agent for Breast Cancer

PLoS ONE ◽  
2012 ◽  
Vol 7 (2) ◽  
pp. e32521 ◽  
Author(s):  
Abhay kumar Singh ◽  
Ratnakar Singh ◽  
Farhat Naz ◽  
Shyam Singh Chauhan ◽  
Amit Dinda ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Therapeutic Agent ◽  
Peptide Inhibitor ◽  
Design And Synthesis ◽  
In Vivo Analysis ◽  
Novel Therapeutic

scholarly journals The Antiviral Effect of Novel Steroidal Derivatives on Flaviviruses

2021 ◽  
Vol 12 ◽  
Author(s):  
Luping Zhang ◽  
Dengyuan Zhou ◽  
Qiuyan Li ◽  
Shuo Zhu ◽  
Muhammad Imran ◽  
...  
Keyword(s):  
Antiviral Effect ◽  
Therapeutic Drug ◽  
Dependent Manner ◽  
Design And Synthesis ◽  
Invasion Stage ◽  
Synthetic Derivatives ◽  
Dose Dependent ◽  
The Brain

Flaviviruses are the major emerging arthropod-borne pathogens globally. However, there is still no practical anti-flavivirus approach. Therefore, existing and emerging flaviviruses desperately need active broad-spectrum drugs. In the present study, the antiviral effect of steroidal dehydroepiandrosterone (DHEA) and 23 synthetic derivatives against flaviviruses such as Japanese encephalitis virus (JEV), Zika virus (ZIKV), and Dengue virus (DENV) were appraised by examining the characteristics of virus infection both in vitro and in vivo. Our results revealed that AV1003, AV1004 and AV1017 were the most potent inhibitors of flavivirus propagation in cells. They mainly suppress the viral infection in the post-invasion stage in a dose-dependent manner. Furthermore, orally administered compound AV1004 protected mice from lethal JEV infection by increasing the survival rate and reducing the viral load in the brain of infected mice. These results indicate that the compound AV1004 might be a potential therapeutic drug against JEV infection. These DHEA derivatives may provide lead scaffolds for further design and synthesis of potential anti-flavivirus potential drugs.

FimH Antagonists for the Oral Treatment of Urinary Tract Infections: From Design and Synthesis to in Vitro and in Vivo Evaluation

2010 ◽  
Vol 53 (24) ◽  
pp. 8627-8641 ◽  
Author(s):  
Tobias Klein ◽  
Daniela Abgottspon ◽  
Matthias Wittwer ◽  
Said Rabbani ◽  
Janno Herold ◽  
...  
Keyword(s):  
Urinary Tract ◽  
Urinary Tract Infections ◽  
Oral Treatment ◽  
In Vivo Evaluation ◽  
Design And Synthesis ◽  
Tract Infections

scholarly journals A Silkworm Infection Model for In Vivo Study of Glycopeptide Antibiotics

Antibiotics ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 300
Author(s):  
Aurora Montali ◽  
Francesca Berini ◽  
Maurizio Francesco Brivio ◽  
Maristella Mastore ◽  
Alessio Saviane ◽  
...  
Keyword(s):  
First Generation ◽  
Bacterial Load ◽  
Larval Survival ◽  
Infection Model ◽  
Glycopeptide Antibiotics ◽  
Cell Wall Assembly ◽  
Aureus Infection ◽  
Peptide Expression ◽  
Antimicrobial Peptide Expression

Glycopeptide antibiotics (GPAs) are drugs of last resort for treating infections by Gram-positive bacteria. They inhibit bacterial cell wall assembly by binding to the d-Ala-d-Ala terminus of peptidoglycan precursors, leading to cell lysis. Vancomycin and teicoplanin are first generation GPAs, while dalbavancin is one of the few, recently approved, second generation GPAs. In this paper, we developed an in vivo insect model to compare, for the first time, the efficacy of these three GPAs in curing Staphylococcus aureus infection. Differently from previous reports, Bombyx mori larvae were reared at 37 °C, and the course of infection was monitored, following not only larval survival, but also bacterial load in the insect body, hemocyte activity, phenoloxidase activity, and antimicrobial peptide expression. We demonstrated that the injection of S. aureus into the hemolymph of B. mori larvae led to a marked reduction of their survival rate within 24–48 h. GPAs were not toxic to the larvae and cured S. aureus infection. Dalbavancin was more effective than first generation GPAs. Due to its great advantages (i.e., easy and safe handling, low rearing costs, low antibiotic amount needed for the tests, no restrictions imposed by ethical and regulatory issues), this silkworm infection model could be introduced in preclinical phases—prior to the use of mice—accelerating the discovery/development rate of novel GPAs.

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