Antioxidants are compounds that inhibit oxidation,a chemical reaction that can produce free radicals. Autoxidation leads to degradation of organic compounds,including living matter. Antioxidants are frequently added to industrial products,such as polymers,fuels,and lubricants,to extend their usable lifetimes. Foods are also treated with antioxidants to forestall spoilage,in particular the rancidification of oils and fats. In cells,antioxidants such as glutathione,mycothiol,or bacillithiol,and enzyme systems like superoxide dismutase,can prevent damage from oxidative stress.
Glutathione is an organic compound with the chemical formula HOCOCH(NH2)CH2CH2CONHCH(CH2SH)CONHCH2COOH. It is is an antioxidant in plants,animals,fungi,and some bacteria and archaea. Glutathione is capable of preventing damage to important cellular components caused by sources such as reactive oxygen species,free radicals,peroxides,lipid peroxides,and heavy metals. It is a tripeptide with a gamma peptide linkage between the carboxyl group of the glutamate side chain and cysteine. The carboxyl group of the cysteine residue is attached by normal peptide linkage to glycine.
Glutathione S-transferases (GSTs),previously known as ligandins,are a family of eukaryotic and prokaryotic phase II metabolic isozymes best known for their ability to catalyze the conjugation of the reduced form of glutathione (GSH) to xenobiotic substrates for the purpose of detoxification. The GST family consists of three superfamilies:the cytosolic,mitochondrial,and microsomal—also known as MAPEG—proteins. Members of the GST superfamily are extremely diverse in amino acid sequence,and a large fraction of the sequences deposited in public databases are of unknown function. The Enzyme Function Initiative (EFI) is using GSTs as a model superfamily to identify new GST functions.
Chlorambucil,sold under the brand name Leukeran among others,is a chemotherapy medication used to treat chronic lymphocytic leukemia (CLL),Hodgkin lymphoma,and non-Hodgkin lymphoma. For CLL it is a preferred treatment. It is given by mouth.
Chelerythrine is a benzophenanthridine alkaloid present in the plant Chelidonium majus. It is a potent,selective,and cell-permeable protein kinase C inhibitor in vitro. And an efficacious antagonist of G-protein-coupled CB1 receptors. This molecule also exhibits anticancer qualities and it has served as a base for many potential novel drugs against cancer. Structurally,this molecule has two distinct conformations,one being a positively charged iminium form,and the other being an uncharged form,a pseudo-base.
Histone deacetylase inhibitors are chemical compounds that inhibit histone deacetylases. Since deacetylation of histones produces transcriptionally silenced euchromatin,HDIs can render chromatin more transcriptionally active and induce epigenomic changes.
Glutathione S-transferase P is an enzyme that in humans is encoded by the GSTP1 gene.
Nuclear factor erythroid 2-related factor 2 (NRF2),also known as nuclear factor erythroid-derived 2-like 2,is a transcription factor that in humans is encoded by the NFE2L2 gene. NRF2 is a basic leucine zipper (bZIP) protein that may regulate the expression of antioxidant proteins that protect against oxidative damage triggered by injury and inflammation,according to preliminary research. In vitro,NRF2 binds to antioxidant response elements (AREs) in the promoter regions of genes encoding cytoprotective proteins. NRF2 induces the expression of heme oxygenase 1 in vitro leading to an increase in phase II enzymes. NRF2 also inhibits the NLRP3 inflammasome.
Microsomal glutathione S-transferase 1 is an enzyme that in humans is encoded by the MGST1 gene.
The alpha-7 nicotinic receptor,also known as the α7 receptor,is a type of nicotinic acetylcholine receptor implicated in long-term memory,consisting entirely of α7 subunits. As with other nicotinic acetylcholine receptors,functional α7 receptors are pentameric [i.e.,(α7)5 stoichiometry].
Glutathione S-transferase kappa 1 (GSTK1) is an enzyme that in humans is encoded by the GSTK1 gene which is located on chromosome seven. It belongs to the superfamily of enzymes known as glutathione S-transferase (GST),which are mainly known for cellular detoxification. The GSTK1 gene consists of eight exons and seven introns and although it is a member of the GST family,its structure has been found to be similar to bacterial HCCA (2-hydroxychromene-2-carboxylate) isomerases and bacterial disulphide-bond-forming DsbA oxidoreductase. This similarity has later allowed the enzyme GSTK1 to be renamed to DsbA-L. Research has also suggested that several variations of the GSTK1 gene can be responsible for metabolic diseases and certain types of cancer.
Fisetin (7,3′,4′-flavon-3-ol) is a plant flavonol from the flavonoid group of polyphenols. It can be found in many plants,where it serves as a yellow/ochre colouring agent. It is also found in many fruits and vegetables,such as strawberries,apples,persimmons,onions and cucumbers. Its chemical formula was first described by Austrian chemist Josef Herzig in 1891.
The alpha-3 beta-4 nicotinic receptor,also known as the α3β4 receptor and the ganglion-type nicotinic receptor,is a type of nicotinic acetylcholine receptor,consisting of α3 and β4 subunits. It is located in the autonomic ganglia and adrenal medulla,where activation yields post- and/or presynaptic excitation,mainly by increased Na+ and K+ permeability.
Ruthenium anti-cancer drugs are coordination complexes of ruthenium complexes that have anticancer properties. They promise to provide alternatives to platinum-based drugs for anticancer therapy. No ruthenium anti-cancer drug has been commercialized.
Reductive stress (RS) is defined as an abnormal accumulation of reducing equivalents despite being in the presence of intact oxidation and reduction systems. A redox reaction involves the transfer of electrons from reducing agents (reductants) to oxidizing agents (oxidants) and redox couples are accountable for the majority of the cellular electron flow. RS is a state where there are more reducing equivalents compared to reductive oxygen species (ROS) in the form of known biological redox couples such as GSH/GSSG,NADP+/NADPH,and NAD+/NADH. Reductive stress is the counterpart to oxidative stress,where electron acceptors are expected to be mostly reduced. Reductive stress is likely derived from intrinsic signals that allow for the cellular defense against pro-oxidative conditions. There is a feedback regulation balance between reductive and oxidative stress where chronic RS induce oxidative species (OS),resulting in an increase in production of RS,again.
EF-24 is a compound that is a synthetic analogue of curcumin,a bioactive phytochemical from turmeric. Curcumin has antioxidant,antibiotic,anti-inflammatory and anti-cancer properties in vitro but has low potency and very poor bioavailability when taken orally,resulting in limited efficacy. EF-24 was developed to try to improve upon these properties,and has been found to be around 10 times more potent than curcumin and with much higher systemic bioavailability. It has never been developed for medical use,though research continues to investigate whether it may be useful as an adjuvant treatment for some cancers alongside conventional chemotherapy drugs.
Conventional drug delivery is limited by the inability to control dosing,target specific sites,and achieve targeted permeability. Traditional methods of delivering therapeutics to the body experience challenges in achieving and maintaining maximum therapeutic effect while avoiding the effects of drug toxicity. Many drugs that are delivered orally or parenterally do not include mechanisms for sustained release,and as a result they require higher and more frequent dosing to achieve any therapeutic effect for the patient. As a result,the field of drug delivery systems developed into a large focus area for pharmaceutical research to address these limitations and improve quality of care for patients. Within the broad field of drug delivery,the development of stimuli-responsive drug delivery systems has created the ability to tune drug delivery systems to achieve more controlled dosing and targeted specificity based on material response to exogenous and endogenous stimuli.
Reduction-sensitive nanoparticles (RSNP) consist of nanocarriers that are chemically responsive to reduction. Drug delivery systems using RSNP can be loaded with different drugs that are designed to be released within a concentrated reducing environment,such as the tumor-targeted microenvironment. Reduction-Sensitive Nanoparticles provide an efficient method of targeted drug delivery for the improved controlled release of medication within localized areas of the body.
Famitinib is a tyrosine kinase receptor inhibitor developed by Jiangsu Hengrui for a variety of cancers.
Danyelle M. Townsend is a biomedical scientist,and academic. She is a Professor and acting Department Chair of Drug Discovery and Biomedical Sciences at the Medical University of South Carolina (MUSC).
