87140-29-2Relevant articles and documents
Interaction between Glutathione and Resveratrol in the Presence of Hydrogen Peroxide: A Kinetic Model
Zinatullina,Kasaikina,Khrameeva,Indeykina,Kononikhin
, p. 255 - 263 (2021/04/26)
Abstract: The kinetics of interaction between glutathione (GSH) and unsaturated phenol resveratrol (RVT) in deionized water in the presence of hydrogen peroxide (H2O2) is studied. At a physiological concentration (0.1–10 mM), GSH containing two carboxyl groups forms acidic solutions (pH of 3–4); the GSH molecules are associated into dimers. Under these conditions, GSH is quite slowly oxidized by atmospheric oxygen, and the reaction between GSH and H2O2 is accompanied by the formation of radicals. The thiyl radical initiation rate (Wi) is a few fractions of a percent of the GSH consumption rate; however, it is sufficient to initiate a thiol–ene chain reaction between GSH and RVT. Using the experimental data on the kinetics and the product composition and the published data on reactions of GSH with H2O2 and thiyl radicals, a kinetic model of the complex interaction between GSH and RVT in the presence of H2O2 in an aqueous medium at 37°C is proposed. The model includes 19 quasi-elementary reactions with respective rate constants, in particular, the formation of intermediate GSH–H2O2 and GSH–GSH complexes, the formation of radicals, and their subsequent transformations into final products in reactions with RVT and GSH. A computer simulation based on the developed model adequately describes the features of the process kinetics in a wide reactant concentration range.
Single-Atom Pd Nanozyme for Ferroptosis-Boosted Mild-Temperature Photothermal Therapy
Chang, Mengyu,Hou, Zhiyao,Li, Chunxia,Li, Fang,Lin, Jun,Liu, Donglian,Peng, Tieli,Wang, Man,Wang, Ruifeng,Yang, Chunzheng
supporting information, p. 12971 - 12979 (2021/05/03)
Photothermal therapy (PTT) is an extremely promising tumor therapeutic modality. However, excessive heat inevitably injures normal tissues near tumors, and the damage to cancer cells caused by mild hyperthermia is easily repaired by stress-induced heat shock proteins (HSPs). Thus, maximizing the PTT efficiency and minimizing the damage to healthy tissues simultaneously by adopting appropriate therapeutic temperatures is imperative. Herein, an innovative strategy is reported: ferroptosis-boosted mild PTT based on a single-atom nanozyme (SAzyme). The Pd SAzyme with atom-economical utilization of catalytic centers exhibits peroxidase (POD) and glutathione oxidase (GSHOx) mimicking activities, and photothermal conversion performance, which can result in ferroptosis featuring the up-regulation of lipid peroxides (LPO) and reactive oxygen species (ROS). The accumulation of LPO and ROS provides a powerful approach for cleaving HSPs, which enables Pd SAzyme-mediated mild-temperature PTT.
Growth Factor-Decorated Ti3C2 MXene/MoS2 2D Bio-Heterojunctions with Quad-Channel Photonic Disinfection for Effective Regeneration of Bacteria-Invaded Cutaneous Tissue
Yang, Zhaopu,Fu, Xinliang,Ma, Daichuan,Wang, Yulin,Peng, Liming,Shi, Jiacheng,Sun, Jiyu,Gan, Xueqi,Deng, Yi,Yang, Weizhong
, (2021/11/01)
Phototherapy has recently emerged as a competent alternative for combating bacterial infection without antibiotic-resistance risk. However, owing to the bacterial endogenous antioxidative glutathione (GSH), the exogenous reactive oxygen species (ROS) generated by phototherapy can hardly behave desired antibacterial effect. To address the daunting issue, a quad-channel synergistic antibacterial nano-platform of Ti3C2 MXene/MoS2 (MM) 2D bio-heterojunctions (2D bio-HJs) are devised and fabricated, which possess photothermal, photodynamic, peroxidase-like (POD-like), and glutathione oxidase-like properties. Under near-infrared (NIR) laser exposure, the 2D bio-HJs both yield localized heating and raise extracellular ROS level, leading to bacterial inactivation. Synchronously, Mo4+ ions can easily invade into ruptured bacterial membrane, arouse intracellular ROS, and deplete intracellular GSH. Squeezed between the “ROS hurricane” from both internal and external sides, the bacteria are hugely slaughtered. After being further loaded with fibroblast growth factor-21 (FGF21), the 2D bio-HJs exhibit benign cytocompatibility and boost cell migration in vitro. Notably, the in vivo evaluations employing a mouse-infected wound model demonstrate the excellent photonic disinfection towards bacterial infection and accelerated wound healing. Overall, this work provides a powerful nano-platform for the effective regeneration of bacteria-invaded cutaneous tissue using 2D bio-HJs.
Reduction of an asymmetric Pt(IV) prodrug fac-[Pt(dach)Cl3(OC(=O)CH3)] by biological thiol compounds: kinetic and mechanistic characterizations
Huo, Shuying,Ma, Dongying,Song, Changying,Sun, Jingjing,Wang, Yafang
, p. 623 - 631 (2021/11/22)
An asymmetric Pt(IV) prodrug fac-[Pt (dach)Cl3(OC(=O)CH3)] (dach = 1,2-diaminocyclohexane) was synthesized, and the reduction of the Pt(IV) prodrug by three biological thiols glutathione (GSH), cysteine (Cys) and homocysteine (Hcy) was investigated by a stopped-flow spectrometer. All the reductions were followed by an overall second-order reaction with first-order in both [Pt(IV)] and [thiol]. The reduction of the Pt(IV) prodrug occurred through a chloride bridge (Pt-Cl-S) mediated two electron transfer process. Therefore, the coordinated chloride possesses a better bridging effect than the oxygen atom from the coordinated –CH3COO? of the Pt(IV) prodrug. A reactivity trend of k′Cys > k′GSH > k′Hcy is found, illustrating that the reactivity is followed by the trend of Cys > GSH > Hcy in pH 7.4 buffer. Graphical abstract: Transition state is formed between the axially coordinated chloride of the platinum(IV) complex and the sulfur atom from the thiol/thiolate group of Cys/Hcy/GSH.[Figure not available: see fulltext.].
Determination of plasma levels of the active thiol form of the direct-acting PrC-210 ROS-scavenger using a fluorescence-based assay
Dreischmeier, Emma,Fahl, William E.
, (2021/01/14)
PrC-210 is a direct-acting ROS-scavenger. It's active when administered orally, IV, or topically; it has none of the nausea/emesis nor hypotension side effects that have precluded human amifostine use. PrC-210 confers 100% survival to mice and rats that received an otherwise 100% lethal radiation dose and 36% reduction of ischemia-reperfusion-induced mouse myocardial infarct damage, and thus is a viable candidate to prevent human ROS-induced ischemia-reperfusion and ionizing radiation toxicities. We report the first assay for the pharmacologically active PrC-210 thiol in blood. PrC-210 has no double-bonds nor light absorption, so derivatizing the thiol with a UV-absorbing fluorochrome enables quantification. This assay: i) is done on the benchtop; it's read with a fluorescence plate reader, ii) provides linear product formation through 60 min, iii) quantifies μM to low mM rodent blood levels of PrC-210 that confer complete radioprotection, iv) accurately reflects PrC-210 thiol formation of mixed disulfides with other thiols in blood, and v) shows excellent between-day assay outcome with very low standard deviation and coefficient of variation. A fluorescence assay quantifying formation of a PrC-210 thiol-bimane adduct enables measurement of blood PrC-210 thiol. A blood assay will help in the development of PrC-210 for use in the human clinical setting.
Alternative mechanisms of action for the apoptotic activity of terpenoid-like chalcone derivatives
Bernardes, Aline,Custodio, Jean M. F.,Molnár, Szilárd,Moura, Andrea F.,Noda-Perez, Caridad,Oliver, Allen G.,Perjési, Pál,Vaz, Wesley F.
supporting information, p. 15267 - 15279 (2021/09/07)
Apoptosis is a defense mechanism against pre-cancerous and infected cells. Although the applicability of β-ionone against diverse cancer cell lines has been exhaustively investigated, the apoptotic activity of terpenoid-like chalcones, as well as their mechanisms of action, is not well understood. Here we present a new terpenoid-like chalcone derivative (I) and its biological potential against HL-60 (leukemia), HCT-116 (colon), and SNB-19 (glioblastoma) cancer cell lines. CompoundIshowed cytotoxicity against over 90% of the tested cell lines. However,Ihas an IC50slightly higher than doxorubicin, a DNA-binding cancer drug, which motivated us to investigate an alternative mechanism of action forIother than DNA-mediated. We performed anin silicostructure-based pharmacophoric screening against various proteins, which indicated mitogen-activated protein kinase 5 (MAP3K5) as a potential protein target. CompoundIwas docked within its active site and was predicted to bind MAP3K5 with a comparable affinity to IM6, a cocrystallized ligand. Finally, we describe the reaction of a reduced glutathione adduct (GSH) with compoundIand previously published derivatives bearing the substitutions 4-chloro (II), 4-bromo (III), and 4-nitro (IV) using HPLC-MS. We show that these are rapid reactions and that the products are stable for up to 24 h. Here, we suggest two alternative mechanisms (MAP3K5 inhibition and thiol reactivity) for the biological potential of a series of terpenoid-like chalcone derivatives. We anticipate that these findings can be explored to design additional derivatives with even more robust apoptotic activity.
Amphiphilic Iodine(III) Reagents for the Lipophilization of Peptides in Water
Hari, Durga Prasad,Mishra, Abhaya Kumar,Tessier, Romain,Waser, Jerome
supporting information, p. 17963 - 17968 (2021/07/20)
We report the functionalization of cysteine residues with lipophilic alkynes bearing a silyl group or an alkyl chain using amphiphilic ethynylbenziodoxolone reagents (EBXs). The reactions were carried out in buffer (pH 6 to 9), without organic co-solvent or removal of oxygen, either at 37 °C or room temperature. The transformation led to a significant increase of peptide lipophilicity and worked for aromatic thiols, homocysteine, cysteine, and peptides containing 4 to 18 amino acids. His6-Cys-Ubiquitin was also alkynylated under physiological conditions. Under acidic conditions, the thioalkynes were converted into thioesters, which could be cleaved in the presence of hydroxylamine.
REAL-TIME MONITORING OF IN VIVO FREE RADICAL SCAVENGERS THROUGH HYPERPOLARIZED N-ACETYL CYSTEINE ISOTOPES
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Paragraph 0148-0150, (2021/07/24)
A method of diagnosing or monitoring a patient suffering from cancer, the method comprising: administering a pharmaceutical composition comprising an effective amount of an active agent, wherein the active agent is [1-13C] N-acetyl cysteine, a deuterated derivative thereof, a pharmaceutically acceptable salt of any of the foregoing thereof, or a combination thereof, together with a pharmaceutically acceptable carrier to the patient; and diagnosing or monitoring the patient by hyperpolarized 13C-MRI. Also disclosed is a method of synthesizing [1-13C] N-acetyl cysteine or a deuterated derivative thereof.
The thiol-based reduction of Bi(V) and Sb(V) anti-leishmanial complexes
Duffin, Rebekah N.,Stephens, Liam J.,Blair, Victoria L.,Kedzierski, Lukasz,Andrews, Philip C.
, (2021/05/10)
Low molecular weight thiols including trypanothione and glutathione play an important function in the cellular growth, maintenance and reduction of oxidative stress in Leishmania species. In particular, parasite specific trypanothione has been established as a prime target for new anti-leishmania drugs. Previous studies into the interaction of the front-line Sb(V) based anti-leishmanial drug meglumine antimoniate with glutathione, have demonstrated that a reduction pathway may be responsible for its effective and selective nature. The new suite of organometallic complexes, of general formula [MAr3(O2CR)2] (M = Sb or Bi) have been shown to have potential as new selective drug candidates. However, their behaviour towards the critical thiols glutathione and trypanothione is still largely unknown. Using NMR spectroscopy and mass spectrometry we have examined the interaction of the analogous Sb(V) and Bi(V) organometallic complexes, [SbPh3(O2CCH2(C6H4CH3))2] S1 and [BiPh3(O2CCH2(C6H4CH3))2] B1, with the trifluoroacetate (TFA) salt of trypanothione and L-glutathione. In the presence of trypanothione or glutathione at the clinically relevant pH of 4–5 for Leishmania amastigotes, both complexes undergo facile and rapid reduction, with no discernible difference. However, at a higher pH (6–7), the complexes behave quite differently towards glutathione. The Bi(V) complex is again reduced rapidly but the Sb(V) complex undergoes slow reduction over 8 h (t1/2 = 54 min.) These results give the first insights into why the highly oxidising Bi(V) complexes display low selectivity in their cytotoxicity towards leishmanial and mammalian cells, while the Sb(V) complexes show good selectivity.
Generation of cyclic glutathione via the thiolactonization of glutathione and identification of a new radical scavenging mechanism
Tsutsui, Ayumi,Morishita, Yuta,Furumachi, Hiyori,Fujimoto, Takashi,Hirai, Rina,Fujita, Tomoyuki,Machinami, Tomoya
, (2021/03/01)
Glutathione (GSH) has two important biological activities, GSH conjugation and radical scavenging. In this work, we determined that GSH can participate in an intramolecular cyclization between the glutamic α-carboxylic acid and the cysteinyl thiol moiety under aqueous conditions. Moreover, we showed that the cyclic glutathione (cGSH) product had more potent radical scavenging activity than GSH. The cGSH radical scavenging activity occurred via a mechanism that differed from that of GSH.
