scholarly journals Marine Spirotetronates: Biosynthetic Edifices That Inspire Drug Discovery

Marine Drugs ◽  
2019 ◽  
Vol 17 (4) ◽  
pp. 232 ◽  
Author(s):  
Alexander A. Braddock ◽  
Emmanuel A. Theodorakis
Keyword(s):  
Drug Discovery ◽  
Solid Tumors ◽  
Antimicrobial Properties ◽  
Structure Optimization ◽  
Class Ii ◽  
Clinical Applications ◽  
Complex Structures ◽  
Antibiotic Resistant ◽  
Synthetic Routes

Spirotetronates are actinomyces-derived polyketides that possess complex structures and exhibit potent and unexplored bioactivities. Due to their anticancer and antimicrobial properties, they have potential as drug hits and deserve further study. In particular, abyssomicin C and tetrocarcin A have shown significant promise against antibiotic-resistant S. aureus and tuberculosis, as well as for the treatment of various lymphomas and solid tumors. Improved synthetic routes to these compounds, particularly the class II spirotetronates, are needed to access sufficient quantities for structure optimization and clinical applications.

Lead structure optimization of compounds identified to induce differentiation in solid tumors

2018 ◽  
Author(s):  
K Esser ◽  
A Kulik ◽  
A Klinger ◽  
E Fleischer ◽  
H Neubauer ◽  
...  
Keyword(s):  
Solid Tumors ◽  
Structure Optimization ◽  
Lead Structure

scholarly journals The Potential of Human Peptide LL-37 as an Antimicrobial and Anti-Biofilm Agent

Antibiotics ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 650
Author(s):  
Kylen E. Ridyard ◽  
Joerg Overhage
Keyword(s):  
Bacterial Infections ◽  
Antimicrobial Properties ◽  
Cross Resistance ◽  
Resistant Bacteria ◽  
Peptide Antibiotic ◽  
Adaptive Responses ◽  
Antibiotic Resistant ◽  
Structural Modifications ◽  
Immobilization Techniques ◽  
Conventional Antibiotics

The rise in antimicrobial resistant bacteria threatens the current methods utilized to treat bacterial infections. The development of novel therapeutic agents is crucial in avoiding a post-antibiotic era and the associated deaths from antibiotic resistant pathogens. The human antimicrobial peptide LL-37 has been considered as a potential alternative to conventional antibiotics as it displays broad spectrum antibacterial and anti-biofilm activities as well as immunomodulatory functions. While LL-37 has shown promising results, it has yet to receive regulatory approval as a peptide antibiotic. Despite the strong antimicrobial properties, LL-37 has several limitations including high cost, lower activity in physiological environments, susceptibility to proteolytic degradation, and high toxicity to human cells. This review will discuss the challenges associated with making LL-37 into a viable antibiotic treatment option, with a focus on antimicrobial resistance and cross-resistance as well as adaptive responses to sub-inhibitory concentrations of the peptide. The possible methods to overcome these challenges, including immobilization techniques, LL-37 delivery systems, the development of LL-37 derivatives, and synergistic combinations will also be considered. Herein, we describe how combination therapy and structural modifications to the sequence, helicity, hydrophobicity, charge, and configuration of LL-37 could optimize the antimicrobial and anti-biofilm activities of LL-37 for future clinical use.

scholarly journals Targeting KRAS mutations with HLA class II-restricted TCRs for the treatment of solid tumors

2021 ◽  
Vol 10 (1) ◽  
pp. 1936757
Author(s):  
Pierre Dillard ◽  
Nicholas Casey ◽  
Sylvie Pollmann ◽  
Patrik Vernhoff ◽  
Gustav Gaudernack ◽  
...  
Keyword(s):  
Solid Tumors ◽  
Class Ii ◽  
Hla Class Ii ◽  
Kras Mutations

Clinical Trials and Machine Learning: Regulatory Approach Review

2021 ◽  
Vol 16 ◽  
Author(s):  
Diego Alejandro Dri ◽  
Maurizio Massella ◽  
Donatella Gramaglia ◽  
Carlotta Marianecci ◽  
Sandra Petraglia
Keyword(s):  
Artificial Intelligence ◽  
Machine Learning ◽  
Clinical Trials ◽  
Patient Safety ◽  
Drug Discovery ◽  
Clinical Applications ◽  
Clinical Development ◽  
Regulatory Approach ◽  
National Competent Authorities ◽  
Review Current

: Machine Learning, a fast-growing technology, is an application of Artificial Intelligence that has significantly contributed to drug discovery and clinical development. In the last few years, the number of clinical applications based on Machine Learning has constantly been growing. Moreover, it is now also impacting National Competent Authorities during the assessment of most recently submitted Clinical Trials that are designed, managed, or generating data deriving from the use of Machine Learning or Artificial Intelligence technologies. We review current information available on the regulatory approach to Clinical Trials and Machine Learning. We also provide inputs for further reasoning and potential indications, including six actionable proposals for regulators to proactively drive the upcoming evolution of Clinical Trials within a strong regulatory framework, focusing on patient safety, health protection, and fostering immediate access to effective treatments.

scholarly journals Bacteriophages: the possible solution to treat infections caused by pathogenic bacteria

2017 ◽  
Vol 63 (11) ◽  
pp. 865-879 ◽  
Author(s):  
Ayman El-Shibiny ◽  
Salma El-Sahhar
Keyword(s):  
Bacterial Infections ◽  
Pathogenic Bacteria ◽  
Phage Therapy ◽  
Multidrug Resistant ◽  
Clinical Applications ◽  
Western World ◽  
Resistant Bacteria ◽  
Vaccine Production ◽  
Bacterial Populations ◽  
Antibiotic Resistant

Since their discovery in 1915, bacteriophages have been used to treat bacterial infections in animals and humans because of their unique ability to infect their specific bacterial hosts without affecting other bacterial populations. The research carried out in this field throughout the 20th century, largely in Georgia, part of USSR and Poland, led to the establishment of phage therapy protocols. However, the discovery of penicillin and sulfonamide antibiotics in the Western World during the 1930s was a setback in the advancement of phage therapy. The misuse of antibiotics has reduced their efficacy in controlling pathogens and has led to an increase in the number of antibiotic-resistant bacteria. As an alternative to antibiotics, bacteriophages have become a topic of interest with the emergence of multidrug-resistant bacteria, which are a threat to public health. Recent studies have indicated that bacteriophages can be used indirectly to detect pathogenic bacteria or directly as biocontrol agents. Moreover, they can be used to develop new molecules for clinical applications, vaccine production, drug design, and in the nanomedicine field via phage display.

scholarly journals Towards the Immunogenic Hyperthermic Action: Modulated ElectroHyperthermia

2020 ◽  
pp. 1-6
Author(s):  
Andras Szasz ◽  
Andras Szasz
Keyword(s):  
Cancer Cells ◽  
Solid Tumors ◽  
Phase Ii ◽  
Immune Cells ◽  
Genetic Information ◽  
Clinical Applications ◽  
Clinical Use ◽  
Hyperthermia Treatment ◽  
Broad Perspective ◽  
Trade Name

Hyperthermia treatment for solid tumors is a long-used, but poorly accepted method in clinical use. Modulated electro-hyperthermia (mEHT, trade name: oncothermia®) changes the paradigm, introduces a novel, cellularly selective and immunogenic cell-ruination. The mEHT method produces tumor-vaccination, presenting the unharmed genetic information of cancer cells to immune cells [1]. The mEHT method is approved in more than 30 countries. Its phase II/III clinical applications indicate a broad perspective.

scholarly journals Beyond fecal microbiota transplantation: Developing drugs from the microbiome

2020 ◽  
Author(s):  
Ylaine Gerardin ◽  
Sonia Timberlake ◽  
Jessica R Allegretti ◽  
Mark B Smith ◽  
Zain Kassam
Keyword(s):  
Public Health ◽  
Drug Discovery ◽  
Infectious Diseases ◽  
Health Outcomes ◽  
Patient Care ◽  
Fecal Microbiota Transplantation ◽  
Fecal Microbiota ◽  
Resistant Bacteria ◽  
Antibiotic Resistant Bacteria ◽  
Antibiotic Resistant

Abstract The transfer of live gut microbes may transform patient care across a range of autoimmune, metabolic, hepatic and infectious diseases. One early approach, fecal microbiota transplantation, has shown promise in Clostridiodes difficile infection and the potential for improving clinical and public health outcomes for other antibiotic-resistant bacteria. These clinical successes have motivated the development of microbiome drugs, which will need to address challenges in safety, uniformity, and delivery while seeking to preserve the benefits of using whole microbiome communities as novel therapeutics and an innovative platform for drug discovery.

scholarly journals Pushing the Frontiers of Accessible Chemical Space to Unleash Design Creativity and Accelerate Drug Discovery

2020 ◽  
Vol 74 (10) ◽  
pp. 803-807
Author(s):  
Thomas C. Fessard ◽  
Kristina Goncharenko ◽  
Quentin Lefebvre ◽  
Christophe Salomé
Keyword(s):  
Drug Discovery ◽  
Small Molecule ◽  
Chemical Space ◽  
Molecular Structures ◽  
Complex Structures ◽  
Small Molecule Drug ◽  
Design Creativity ◽  
Research Environments ◽  
Complex Structural ◽  
Synthetic Methodologies

In highly competitive research environments, the ability to access more complex structural spaces efficiently is a predictor of a company's ability to generate novel IP-protected small molecule candidates with adequate properties, hence filling their development pipelines. SpiroChem is consistently developing new synthetic methodologies and strategies to access complex molecular structure, thereby facilitating and accelerating small molecule drug discovery. Pushing the limits of what are perceived as complex molecular structures allows SpiroChem and its clients to unleash creativity and explore meaningful chemical spaces, which are under-exploited sources of novel active molecules. In this article, we explain how we differentiated ourselves in a globalized R&D environment and we provide several snapshots of how efficient methodologies can generate complex structures, rapidly.

scholarly journals Development of Robust Chitosan–Silica Class II Hybrid Coatings with Antimicrobial Properties for Titanium Implants

Coatings ◽  
2020 ◽  
Vol 10 (6) ◽  
pp. 534 ◽  
Author(s):  
Zach Gouveia ◽  
Hiran Perinpanayagam ◽  
Jesse Zhu
Keyword(s):  
Antimicrobial Properties ◽  
Class Ii ◽  
Magic Angle Spinning ◽  
Titanium Implants ◽  
Hybrid Coatings ◽  
Homogeneous Distribution ◽  
Magic Angle ◽  
Coating Materials ◽  
Angle Spinning ◽  
Tensile Adhesion

The purpose of this study was to develop robust class II organic–inorganic films as antibacterial coatings on titanium alloy (Ti6Al4V) implants. Coating materials were prepared from organic chitosan (20–80 wt.%) coupled by 3-glycydoxytrimethoxysilane (GPTMS) with inorganic tetraethoxysilane (TEOS). These hybrid networks were imbedded with antimicrobial silver nanoparticles (AgNPs) and coated onto polished and acid-etched Ti6Al4V substrates. Magic-angle spinning nuclear magnetic resonance (13CMAS-NMR), attenuated total reflectance Fourier-transform infrared spectroscopy (ATR-FTIR) and the ninhydrin assay, confirmed the presence and degree of covalent crosslinking (91%) between chitosan and GPTMS. Scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDS) identified surface roughness and microtopography on thin films and confirmed homogeneous distribution of elements throughout the coating. Cross-hatch and tensile adhesion testing demonstrated the robustness and adherence (15–20 MPa) of hybrid coatings to acid-etched titanium substrates. Staphylococcus aureus and Escherichia coli cultures and their biofilm formation were inhibited by all hybrid coatings. Antibacterial effects increased markedly for coatings loaded with AgNPs and appeared to increase with chitosan content in biofilm assays. These results are promising in the development of class II hybrid materials as robust and highly adherent antibacterial films on Ti6Al4V implants.

scholarly journals Feature Issue Introduction: Bio-Optics in Clinical Applications, Nanotechnology, and Drug Discovery

2010 ◽  
Vol 1 (3) ◽  
pp. 746 ◽  
Author(s):  
Robert J. Nordstrom ◽  
Adah Almutairi ◽  
Elizabeth M.C. Hillman
Keyword(s):  
Drug Discovery ◽  
Clinical Applications
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