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American Journal of Health-system... Jan 2021
Topics: Azo Compounds; Humans; Pyrimidines
PubMed: 33091108
DOI: 10.1093/ajhp/zxaa347 -
Molecules (Basel, Switzerland) Sep 2022Azo molecules, characterized by the presence of a -N=N- double bond, are widely used in various fields due to their sensitivity to external stimuli, ch as light. The... (Review)
Review
Azo molecules, characterized by the presence of a -N=N- double bond, are widely used in various fields due to their sensitivity to external stimuli, ch as light. The emergence of bacterial resistance has pushed research towards designing new antimicrobial molecules that are more efficient than those currently in use. Many authors have attempted to exploit the antimicrobial activity of azobenzene and to utilize their photoisomerization for selective control of the bioactivities of antimicrobial molecules, which is necessary for antibacterial therapy. This review will provide a systematic and consequential approach to coupling azobenzene moiety with active antimicrobial molecules and drugs, including small and large organic molecules, such as peptides. A selection of significant cutting-edge articles collected in recent years has been discussed, based on the structural pattern and antimicrobial performance, focusing especially on the photoactivity of azobenzene and the design of smart materials as the most targeted and desirable application.
Topics: Anti-Bacterial Agents; Anti-Infective Agents; Azo Compounds
PubMed: 36080413
DOI: 10.3390/molecules27175643 -
European Journal of Neurology Jul 2023Spinal muscular atrophy (SMA) is caused by reduced levels of survival of motor neuron (SMN) protein due to deletions and/or mutations in the SMN1 gene. Risdiplam is an... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND AND PURPOSE
Spinal muscular atrophy (SMA) is caused by reduced levels of survival of motor neuron (SMN) protein due to deletions and/or mutations in the SMN1 gene. Risdiplam is an orally administered molecule that modifies SMN2 pre-mRNA splicing to increase functional SMN protein.
METHODS
SUNFISH Part 1 was a dose-finding study conducted in 51 individuals with types 2 and 3 SMA aged 2-25 years. A dose-escalation method was used to identify the appropriate dose for the subsequent pivotal Part 2. Individuals were randomized (2:1) to risdiplam or placebo at escalating dose levels for a minimum 12-week, double-blind, placebo-controlled period, followed by treatment for 24 months. The dose selection for Part 2 was based on safety, tolerability, pharmacokinetic, and pharmacodynamic data. Exploratory efficacy was also measured.
RESULTS
There was no difference in safety findings for all assessed dose levels. A dose-dependent increase in blood SMN protein was observed; a median twofold increase was obtained within 4 weeks of treatment initiation at the highest dose level. The increase in SMN protein was sustained over 24 months of treatment. Exploratory efficacy showed improvement or stabilization in motor function. The pivotal dose selected for Part 2 was 5 mg for patients with a body weight ≥20 kg or 0.25 mg/kg for patients with a body weight <20 kg.
CONCLUSIONS
SUNFISH Part 1 demonstrated a twofold increase in SMN protein after treatment with risdiplam. The observed safety profile supported the initiation of the pivotal Part 2 study. The long-term efficacy and safety of risdiplam are being assessed with ongoing treatment.
Topics: Humans; Muscular Atrophy, Spinal; Pyrimidines; Azo Compounds; RNA Splicing; Transcription Factors
PubMed: 35837793
DOI: 10.1111/ene.15499 -
Journal of Natural Products Nov 2020Azoxy compounds belong to a small yet intriguing group of natural products sharing a common functional group with the general structure RN═N(O)R. Their intriguing... (Review)
Review
Azoxy compounds belong to a small yet intriguing group of natural products sharing a common functional group with the general structure RN═N(O)R. Their intriguing chemical structures, diverse biological activities, and important industrial applications have received attention from researchers in natural product chemistry, total synthesis, and biosynthesis. This review presents current updates about the structural diversity of natural azoxy compounds isolated from different organisms and highlights the enzymes and biological logic involved in their construction. We assume that the identification of key enzymes will provide efficient tools in biocatalysis to generate new azoxy compounds, while genome mining may result in novel natural azoxy compounds of medical and industrial interest.
Topics: Azo Compounds; Biocatalysis; Biological Products
PubMed: 33197183
DOI: 10.1021/acs.jnatprod.0c00725 -
Molecules (Basel, Switzerland) Jan 2020Several series of natural polyphenols are described for their biological and therapeutic potential. Natural stilbenoid polyphenols, such as trans-resveratrol,... (Review)
Review
Several series of natural polyphenols are described for their biological and therapeutic potential. Natural stilbenoid polyphenols, such as trans-resveratrol, pterostilbene and piceatannol are well-known for their numerous biological activities. However, their moderate bio-availabilities, especially for trans-resveratrol, prompted numerous research groups to investigate innovative and relevant synthetic resveratrol derivatives. This review is focused on isosteric resveratrol analogs aza-stilbenes and azo-stilbenes in which the C=C bond between both aromatic rings was replaced with C=N or N=N bonds, respectively. In each series, synthetic ways will be displayed, and structural sights will be highlighted and compared with those of resveratrol. The biological activities of some of these molecules will be presented as well as their potential therapeutic applications. In some cases, structure-activity relationships will be discussed.
Topics: Antioxidants; Aza Compounds; Azo Compounds; Molecular Structure; Resveratrol; Stereoisomerism; Stilbenes; Structure-Activity Relationship
PubMed: 32019195
DOI: 10.3390/molecules25030605 -
Food and Chemical Toxicology : An... Aug 2023Azo compounds are widely distributed synthetic chemicals in the modern world. Their most important applications are as dyes, but, in addition, several azo compounds are... (Review)
Review
Azo compounds are widely distributed synthetic chemicals in the modern world. Their most important applications are as dyes, but, in addition, several azo compounds are used as pharmaceuticals. Ingested azo compounds can be reduced by the action of bacteria in the gut, where the oxygen tension is low, and the development of microbiome science has allowed more precise delineation of the roles of specific bacteria in these processes. Reduction of the azo bond of an azo compound generates two distinct classes of aromatic amine metabolites: the starting material that was used in the synthesis of the azo compound and a product which is formed de novo by metabolism. Reductive metabolism of azo compounds can have toxic consequences, because many aromatic amines are toxic/genotoxic. In this review, we discuss aspects of the development and application of azo compounds in industry and medicine. Current understanding of the toxicology of azo compounds and their metabolites is illustrated with four specific examples - Disperse Dyes used for dyeing textiles; the drugs phenazopyridine and eltrombopag; and the ubiquitous food dye, tartrazine - and knowledge gaps are identified. SUBMISSION TO: FCT VSI: Toxicology of Dyes.
Topics: Azo Compounds; Coloring Agents; Tartrazine; Bacteria; Amines
PubMed: 37451600
DOI: 10.1016/j.fct.2023.113932 -
Journal of Controlled Release :... May 2022Azobenzene-based molecules show unique trans-cis isomerization upon ultraviolet light irradiation, which induce the change of polarity, crystallinity, stability, and... (Review)
Review
Azobenzene-based molecules show unique trans-cis isomerization upon ultraviolet light irradiation, which induce the change of polarity, crystallinity, stability, and binding affinity with pharmacological target. Moreover, azobenzene is the substrate of azoreductase that is often overexpressed in many pathological sites, e.g. hypoxic solid tumor. Therefore, azobenzene can be a multifunctional molecule in material science, pharmaceutical science and biomedicine because of its sensitivity to light, hypoxia and certain enzymes, hence showing potential application in site-specific smart therapy. Herein we focus on the employment of azobenzene and its derivatives for engineering triggered prodrugs and drug delivery systems, and provide an overview of photoswitchable azo-based prodrugs, the associated problems regarding the reversible isomerization and tissue penetration of ultraviolet (UV) light, as well as the potential solutions. We also present the advance of azo-bearing delivery vehicles wherein azobenzene acts as the linker, capping agent, and building block, and discuss the corresponding mechanisms for controlled cargo release, endocytosis enhancement and sensitization of free radical cancer therapy.
Topics: Azo Compounds; Drug Delivery Systems; Prodrugs; Ultraviolet Rays
PubMed: 35339578
DOI: 10.1016/j.jconrel.2022.03.041 -
Chemistry & Biodiversity Nov 2021Bacteria can produce nitrogenous compounds via both primary and secondary metabolic processes. Many bacterial volatile nitrogenous compounds produced during the... (Review)
Review
Bacteria can produce nitrogenous compounds via both primary and secondary metabolic processes. Many bacterial volatile nitrogenous compounds produced during the secondary metabolism have been identified and reported for their antioxidant, antibacterial, antifungal, algicidal and antitumor activities. The production of these nitrogenous compounds depends on several factors, including the composition of culture media, growth conditions, and even the organic solvent used for their extraction, thus requiring their identification in specific conditions. In this review, we describe the volatile nitrogenous compounds produced by bacteria especially focusing on their antimicrobial activity. We concentrate on azo-compounds mainly pyrazines and pyrrolo-pyridines reported for their activity against several microorganisms. Whenever significant, extraction and identification methods of these compounds are also mentioned and discussed. To the best of our knowledge, this is first review describing volatile nitrogenous compounds from bacteria focusing on their biological activity.
Topics: Anti-Bacterial Agents; Azo Compounds; Bacteria; Microbial Sensitivity Tests; Molecular Structure; Volatile Organic Compounds
PubMed: 34643327
DOI: 10.1002/cbdv.202100549 -
Current Opinion in Structural Biology Aug 2019Chemical and electrical signaling at the synapse is a dynamic process that is crucial to neurotransmission and pathology. Traditional pharmacotherapy has found countless... (Review)
Review
Chemical and electrical signaling at the synapse is a dynamic process that is crucial to neurotransmission and pathology. Traditional pharmacotherapy has found countless applications in both academic labs and the clinic; however, diffusible drugs lack spatial and temporal precision when employed in heterogeneous tissues such as the brain. In the field of photopharmacology, chemical attachment of a synthetic photoswitch to a bioactive ligand allows cellular signaling to be controlled with light. Azobenzenes have remained the go-to photoswitch for biological applications due to their tunable photophysical properties, and can be leveraged to achieve reversible optical control of numerous receptors and ion channels. Here, we discuss the most recent advances in photopharmacology which will improve the use of azobenzene-based probes for neuroscience applications.
Topics: Azo Compounds; Drug Design; Light; Molecular Probes; Signal Transduction; Synaptic Transmission
PubMed: 30825844
DOI: 10.1016/j.sbi.2019.01.022 -
Physical Chemistry Chemical Physics :... Oct 2022Diffusion-based translocation along DNA or RNA molecules is essential for genome regulatory proteins to execute their biological functions. The reduced dimensionality of...
Diffusion-based translocation along DNA or RNA molecules is essential for genome regulatory proteins to execute their biological functions. The reduced dimensionality of the searching process makes the proteins bind specific target sites at a "faster-than-diffusion-controlled rate". We herein report a photoresponsive slider-track diffusion system capable of self-assembly rate acceleration, which consists of (-)-camphorsulfonic acid, 4-(4'--octoxylphenylazo)benzenesulfonic acid, and isotactic poly(2-vinylpyridine). The protonated pyridine rings act as the footholds for anionic azo sliders to diffusively bind and slide along polycationic tracks electrostatic interactions. Ultraviolet light triggers the to isomerization and aggregation of azo sliders, which can be monitored by multiple spectroscopic methods without labeling. The presence of vinyl polymer track increases the aggregation rate of azobenzene up to ∼20 times, depending on the stereoregularity of the polymer chain, the acid/base ratio and the addition of salt. This system has a feature of simplicity, monitorability, controllability, and could find applications in designing molecular machines with desired functionalities.
Topics: Azo Compounds; DNA; Polymers; Pyridines; RNA; Ultraviolet Rays
PubMed: 36165176
DOI: 10.1039/d2cp04064f