China
Africa
Explore chapters and articles related to this topic
Enzyme-Responsive Nanomedicine
Published in Lin Zhu, Stimuli-Responsive Nanomedicine, 2021
Hong Wu, SongYan Guo, Tie Hong Yang
Enzymes are highly efficient biological catalysts that play the central roles in various biochemical processes. Enzyme-catalyzed reactions usually occur with high selectivity and efficiency toward enzymes’ substrates under mild physiological or pathological conditions. Enzymes are involved in all biological and metabolic processes, serving as the prime protagonists in the chemistry of living organisms at a molecular level. Moreover, enzymes can be a diagnostic biomarker since the dysregulation of various enzymes is a characteristic feature of numerous diseases [2]. Even in the same host, the pattern of the enzyme activity and expression may be different in different tissues. The expression of certain enzymes like protease, esterase and glycosidase in pathological tissues suffering from inflammation or cancer is often higher compared with that in normal tissues [3]. These enzymes may serve as local stimuli for certain diseases. For example, esterases produced by macrophages are elevated at the site of inflammation. Myeloperoxidase is highly associated with cardiovascular and neurological diseases [4, 5]. Therefore, the disease-specific or tissue-associated enzymes when undergo the abnormal expression can be potential stimuli/targets for the nanocarriers that are programmed to deliver drugs via an enzyme-responsive manner.
Cardiovascular Disease and Oxidative Stress
Published in Peter Grunwald, Pharmaceutical Biocatalysis, 2019
Marco Fernandes, Alisha Patel, Holger Husi
Myeloperoxidase (MPO), a heme protein released by leukocytes, plays a key role in inflammation and oxidative stress. MPO’s anti-microbicidal activity is due to its ability to oxidize chloride (CI−), bromide (Br−), iodine (I−) and thiocyanate (SCN−) by H2O2, thus producing their corresponding hypohalous acids (HOX) (Lazarevic-Pasti et al., 2015). It has become increasingly recognized that MPO performs a very important role as part of the innate immune system through the formation of microbicidal reactive oxidants, whilst it affects the arterial endothelium with a number of mechanisms that include modification of net cellular cholesterol flux and impairment of NO-induced vascular relaxation. Thus, MPO is implicated into both the formation and propagation of atheromatosis and there is substantial evidence that it also promotes ischemia through destabilization of the vulnerable plaque. Numerous studies have added information on the notion that MPO and its oxidant products are part of the inflammatory cascade initiated by endothelial injury and they are significantly overproduced at the site of arterial inflammation. Subsequent studies achieved quantification of this observation showing significant elevations of the systemic levels of MPO in a wide spectrum of cardiovascular disease scenarios with acute coronary syndromes and heart failure being the most studied (Anatoliotakis et al., 2013). There is a positive correlation of MPO plasma levels with severity of coronary artery disease (CAD) within CAD-patients co-exhibiting type 2 diabetes mellitus (T2DM) (Song et al., 2015). In opposition, other study found that five MPO polymorphisms were positively associated with MPO plasma level, but not with cardiovascular mortality (Scharnagl et al., 2014). Other groups have shown the potential role of MPO has as a biomarker for sepsis in the intensive care unit (ICU)(Schrijver et al., 2017) which could aid in the diagnosing of sepsis and/or as predictor of mortality.
Carbon Nanotubes Used as Nanocarriers in Drug and Biomolecule Delivery
Published in Raj K. Keservani, Anil K. Sharma, Rajesh K. Kesharwani, Drug Delivery Approaches and Nanosystems, 2017
Hua He, Deli Xiao, Lien Ai Pham-Huy, Pierre Dramou, Chuong Pham-Huy
CNTs employed for biomedical purposes are in forms of either dispersed or functionalized ones. After introducing to biosystems, it is possible that these CNTs are metabolized into other substances. The metabolism of CNTs definitely affects their biomedical applications and also might lead to unwanted toxicity. Therefore, the in vivo metabolism of CNTs should be highly concerned (Yang et al., 2012). According to Zhang et al. (2011), functionalized SWCNTs seem to be metabolizable in animal body. Yang et al. (2012) found that the skeleton of CNTs is relatively more stable than their functional groups. The stability of CNTs is also reflected by the long-term accumulation in vivo without being metabolized, where CNTs were visualized in mouse organs upon transmission electron microscopy (TEM) at several months postexposure. The stability of carbon skeleton also implies that CNTs are hard to be metabolized to small molecules, which may easily be excreted via urine and feces. In contrast to the stability of carbon skeleton, the functional groups fixed on CNTs by both kinds of covalent and noncovalent functionalization are much easier to fall off from CNTs. Current results suggest that both kinds of functional groups could be detached from CNTs in vivo and this makes functionalized CNTs transformed into less functionalized or pristine CNTs. The metabolism of noncovalently functionalized CNTs is generally regarded as desorption of the suspending reagents. Yang et al. (2012) suggested that the metabolism of CNTs in vivo is organ-dependent, which requires individual evaluation for each accumulation organ. Because of the high stability of carbon skeleton, the metabolism of CNTs mainly means defunctionalization of the surface functional groups. Therefore, the liver is the most possible metabolic organ in body for CNTs. Less functionalized CNTs are believed to be more toxic. Therefore, the hepatic toxicity of CNTs needs more attentions. Comparing the stability of noncovalently and covalently functionalized CNTs in vivo, the covalently functionalized CNTs seem more stable than noncovalently suspended ones. This phenomenon indicates that covalently modified CNTs are more suitable for biomedical use in vivo from the stability view. For the noncovalently suspended CNTs, PEG-PL is preferred among other stable suspending reagents (Yang et al., 2012; Zhang et al., 2010). These findings imply that the biodegradation of CNTs may be a key determinant of the degree and severity of the inflammatory responses in individuals exposed to them. Nevertheless, some scientists have recently shown that CNTs can be broken down by myeloperoxidase (MPO), an enzyme found in neutrophils of mice (Kagan et al., 2010). Their discoveries contradict what was previously believed, that CNTs are not degraded in the body. This action of how MPO converts CNTs into water and carbon dioxide can be significant to toxicology and thus represents a major advance in nanomedicine, since it clearly shows that CNTs can be metabolized by endogenous MPO (He et al., 2013; Singh et al., 2012). However, further studies are still required in order to draw an appropriate conclusion.
One-pot synthesis of novel fused mesoionic compounds: 1-substituted-5-thioxo-5,6-dihydro-[1,2,4]triazolo[1,5-c]quinazolin-1-ium-2-thiolates
Published in Journal of Sulfur Chemistry, 2020
Sergiy M. Kovalenko, Oleksandr G. Drushlyak, Illia O. Mariutsa
Quinazolin-4(3H)-one derivatives are in abundance among pharmacological active materials of natural or synthetic sources. The biological behavior of quinazolinones varies essentially with even minor modifications in their molecular structure [1] and provides diverse pharmacological properties. Depending on the position and nature of substituents, 4-oxoquinazolines exhibit different biological activities such as natural alkaloids [2], antioxidant [3], antimicrobial [1,3–7], antibacterial [8,9], antifungal [10,11], antihypertensive [12–14], anti-inflammatory [15–18], anticonvulsant [19,20], and anticancer [21–27]. Among the variety of quinazolinones, those bearing amino function at the 3 position of the quinazoline ring are of particular interest. So, the introduction at the 3 position, an arylideneamino substituent increases antibacterial action [9]. 3-N-sulfonamides [5] and 3-N-phosphorylated quinazolinones [6,7] seem to be promising antimicrobial agents. 3-N-amides possess anticonvulsant action [19]. On the other hand, 2-thioxoquinazolin-4(3H)-ones [24] and 2-alkylthioquinazolin-4(3H)-ones [26] show promising antitumor activity. Against this background, biological and chemical properties of the N-substituted-N'-(4-oxo-2-thioxo-1,4-dihydroquinazolin-3(2H)-yl)thioureas are insufficiently explored. However, these compounds have recently become interesting as inhibitors of myeloperoxidase and useful for the treatment of inflammatory conditions including neuroinflammatory diseases such as Parkinson’s and Alzheimer’s [28]. Therefore, the initial aim of our investigation is to develop the effective synthesis of (4-oxo-2-thioxo-1,4-dihydroquinazolin-3(2H)-yl)thioureas.
Alteration of thiol-disulfide homeostasis in workers occupationally exposed to arsenic
Published in Archives of Environmental & Occupational Health, 2018
Murat Büyükşekerci, Ceylan Bal, Utku Serkant, Meşide Gündüzöz, Murat Alışık, Engin Tutkun, Ömer Hınç Yılmaz
We measured serum myeloperoxidase (MPO) activity by using a modified version of o-dianisidine method.21 This method is based on kinetic measurement of yellowish-orange compound, the product of ofo-dianisidine and MPO oxidation reaction, at 460 nm. Hydrogen peroxide (H2O2) also presents in the milieu. Degradation of 1 μmol of H2O2 per minute at 25°C is defined as one unit 1U MPO. The unit used for MPO activity was units per liter (U/L)
Effects of β-cyclodextrin-based Schiff-base Zn(II) complexes: synthesis, physicochemical characterization and their role in alleviating oxidative stress related disorder
Published in Journal of Coordination Chemistry, 2018
Ananya Das, Somit Dutta, Biswajit Sinha
Despite its lower reactivity compared to other potential ROS, H2O2 performs an important role to modulate carcinogenesis. H2O2 defused throughout the mitochondria and cell membrane and subsequently generate various types of cellular injury [43, 44]. In the in vivo conditions, hydroxyl radical (OH•) produces 8-hydroxy-guanosine, the hydrolysis product of 8-hydroxydeoxyguanosine (8-OHdG) can attack on DNA and is involved in carcinogenesis progression, especially breast carcinoma [46–48]. Thus, increase in the scavenging activities of H2O2 and OH• by complexes 4a and 4b might facilitate chemoprevention. Spontaneous dismutation of the highly toxic superoxide anion (O2•−) in mitochondria generates singlet oxygen. Generation of singlet oxygen from superoxide anion is one of the primary causes of lipid peroxidation. Lipid peroxidation is the pathogenesis of a wide range of diseases. Initiation of lipid peroxidation is the cause of propagation of chain reaction taking place until termination products are produced. Therefore, the end product malomdialdehyde (MDA), 4-hydroxy-2-nonenol, and F2-isoprostanes were generated from the lipid peroxidation and accumulated in biological system. Accumulation of these toxic products can cause mutation and deletions in both nuclear and mitochondrial DNA. 4-Hydroxy nonenal (4-HNE), the biomarkers of oxidative stress, are important in a number of cancer signaling pathways [49]. The present study demonstrated the significant superoxide anion and lipid peroxidation scavenging capacities by the complexes, thus suggesting a probable protective role against carcinogenesis by the prevention of peroxidase formation. The neutrophilic enzyme, myeloperoxidase, resulting from the oxidation of Cl- ions at the site of inflammation produces hypochlorous acid (HOCl) and causes target cell lyses [50]. The scavenging activity of hypochlorous acid by Zn(II) complexes 4a and 4b appears quite promising and, therefore, might be able to combat inflammation related carcinogenesis.