83730-53-4 | Page 4 of 5 | Heterocyclic Building Blocks-Benzoxazole

Xu, Jiaxi’s team published research in Journal of Colloid and Interface Science in 2022-12-15 | CAS: 83730-53-4

Construction of multifunctional mesoporous silicon nano-drug delivery system and study of dual sensitization of chemo-photodynamic therapy in vitro and in vivo. Recommended basis is Sulfoximine, Bioisosteric. Products is: https://www.ambeed.com/products/50578-18-2.html, 145026-07-9

(2S)-2-Amino-4-(butylsulfonimidoyl)butanoic acid (BD136012) is a building block containing a sulfoximine group. Several CDK and ATR inhibitors have exemplified the utilization of the NH sulfoximine group as abioisostere for a sulfonamide group to overcome the main project hurdles of aqueous solubility, sulfonamide-mediated off-target activity and IP. Moreover, its NH group could be expediently further functionalized through Buchwald-Hartwig coupling reaction and multifarious nucleophilic reactions.. Recommended Products is: 4381-25-3 and 1621962-30-8.

This study was conducted to construct a multifunctional nanodrug delivery system (NDDS) to deplete glutathione (GSH) in tumor cells and amplify oxidative stress, enhancing the synergistic effect of chemotherapy and photodynamic therapy (PDT). L-Buthionine-sulfoximine (BSO) and chlorin e6 (Ce6) were loaded into mesoporous silicon nanoparticles (MSN), and then MSN were modified with oxidized hyaluronic acid (OHA) as a pore-blocking agent. Cisplatin (Pt(II)) was further loaded by a coordination reaction with carboxyl groups in OHA to yield a multifunctional NDDS (denoted as MSN@OHA-Ce6/BSO/Pt). The physicochem. properties and antitumor activity of the prepared nanoparticles were characterized in detail. In vitro and in vivo experiments demonstrated that OHA was shed from MSN@OHA-Ce6/BSO/Pt under acidic conditions in tumors, resulting in the release of free BSO, Ce6, and Pt(II). The released BSO could reduce intracellular GSH expression by 48.8%, effectively enhancing the PDT effect of Ce6 and the chemotherapy effect of Pt(II). Finally, the tumor inhibitory rate (vs saline) reached 73.8% ¡À 2.5% for MSN@OHA-Ce6/BSO/Pt in A549/DDP tumor-bearing nude mice. Therefore, the multifunctional NDDS significantly enhanced the synergistic effect of PDT and chemotherapy.

Referemce:
Benzoxazole – Wikipedia,
Benzoxazole | C7H5NO – PubChem

Guo, Jianshuang’s team published research in Biochemical Pharmacology (Amsterdam, Netherlands) in 2022-06-30 | CAS: 83730-53-4

A rational foundation for micheliolide-based combination strategy by targeting redox and metabolic circuit in cancer cells. Recommended basis is Sulfoximine, Bioisosteric. Products is: https://www.ambeed.com/products/50578-18-2.html, 145026-07-9

Accumulating evidence has supported that targeting oxidative stress and metabolic alterations of cancer is an effective strategy to combat cancer. We previously reported that Dimethylaminomicheliolide (DMAMCL) and its active metabolite micheliolide (MCL) can cause oxidative stress and cell death in leukemia and glioblastoma. However, the detailed mechanism underlying MCL or DMAMCL triggered oxidative stress remains elusive. Herein, using leukemia HL60 cells and glioblastoma U118MG cells as models, we found that MCL-induced oxidative stress is mainly mediated by reduced glutathione (GSH). Overproduced reactive oxygen species (ROS) can lead to oxidative damage to mitochondrial, impairing the ability of the tricarboxylic acid (TCA) cycle and causing dysfunction of mitochondrial respiratory chain. On the other hand, the depletion of GSH activates GSH biosynthesis pathway and has possibility to give rise to more GSH to scavenge ROS in cancer cells. Targeting this redox and metabolic circuit, we identified L-buthionine sulfoximine (BSO), an inhibitor in GSH biosynthesis, as an agent that can enhance MCL regimen to inhibit GSH compensatory event and thereby further facilitate cancer cell oxidative stress. Together, these results illustrate that targeting redox and metabolic pathway by MCL/DMAMCL combination with BSO is a potent therapeutic intervention for the treatments of glioblastoma and acute-myelocytic leukemia.

Referemce:
Benzoxazole – Wikipedia,
Benzoxazole | C7H5NO – PubChem

Sefcikova, Zuzana’s team published research in Reproductive Toxicology in 2021-10-31 | CAS: 83730-53-4

Maternal overweight increased sensitivity of mouse preimplantation embryos to oxidative stress in vitro. Recommended basis is Sulfoximine, Bioisosteric. Products is: https://www.ambeed.com/products/50578-18-2.html, 145026-07-9

The aim of this study was to compare the sensitivity of mouse preimplantation embryos obtained from mothers with different body conditions to an environment with increased oxidative stress. An intergenerational dietary model based on mouse overfeeding during the intrauterine and early postnatal period was used to produce females with increased body fat content (¡Ý 11%). Three different sources of oxidative stress were applied: 0.01 mM 2,2′-Azobis (2-methylpropionamidine) dihydrochloride (AAPH), free radical-generating compound; 5 mM L-Buthionine-sulfoximine (BSO), glutathione synthesis inhibitor; and 0.01 mM Sodium nitroprusside dihydrate (SNP), nitric oxide donor. Two-cell embryos isolated from controls (with 7%-8% body fat content) and overweight mice were cultured in vitro with selected compounds until blastocyst formation. Development of two-cell embryos isolated from overweight dams was neg. affected by the presence of BSO and SNP (P < 0.01). Similar impact was recorded in two-cell embryos obtained from control mothers only after exposure to BSO (P < 0.05). Fluorescence anal. of blastocysts recovered from overweight dams revealed reduced total cell numbers after AAPH and BSO treatment, and increased incidence of cell death after BSO and SNP. In the controls, neg. impact on blastocyst quality, represented by reduced cell number, was observed only after BSO. Immunofluorescence evaluation of freshly-recovered zygotes and two-cell embryos showed that those obtained from overweight dams displayed significantly lower fluorescence signal intensity of Glutathione peroxidase 8 than those from control dams. In conclusion, the results suggest that preimplantation embryos originating from overweight mice might be more vulnerable to oxidative stress than those originating from control females. Maternal overweight increased sensitivity of mouse preimplantation embryos to oxidative stress in vitro. Recommended basis is Sulfoximine, Bioisosteric. Products is: https://www.ambeed.com/products/50578-18-2.html, 145026-07-9

Referemce:
Benzoxazole – Wikipedia,
Benzoxazole | C7H5NO – PubChem

Kim, Ji-Eun’s team published research in Antioxidants in 2022 | CAS: 83730-53-4

Glutathione Regulates GPx1 Expression during CA1 Neuronal Death and Clasmatodendrosis in the Rat Hippocampus following Status Epilepticus. Recommended basis is Sulfoximine, Bioisosteric. Products is: https://www.ambeed.com/products/50578-18-2.html, 145026-07-9

Glutathione peroxidase-1 (GPx1) catalyze the reduction of H2O2 by using glutathione (GSH) as a cofactor. However, the profiles of altered GPx1 expression in response to status epilepticus (SE) have not been fully explored. In the present study, GPx1 expression was transiently decreased in dentate granule cells, while it was temporarily enhanced and subsequently reduced in CA1 neurons following SE. GPx1 expression was also transiently declined in CA1 astrocytes (within the stratum radiatum) following SE. However, it was elevated in reactive CA1 astrocytes, but not in clasmatodendritic CA1 astrocytes, in chronic epilepsy rats. Under physiol. condition, L-buthionine sulfoximine (BSO, an inducer of GSH depletion) increased GPx1 expression in CA1 neurons but decreased it in CA1 astrocytes. However, N-acetylcysteine (NAC, an inducer of GSH synthesis) did not influence GPx1 expression in these cell populations. Following SE, BSO aggravated CA1 neuronal death, concomitant with reduced GPx1 expression. Further. BSO also lowered GPx1 expression in CA1 astrocytes. NAC effectively prevented neuronal death and GPx1 downregulation in CA1 neurons, and restored GPx1 expression to the control level in CA1 astrocytes. In chronic epilepsy rats, BSO reduced GPx1 intensity and exacerbated clasmatodendritic degeneration in CA1 astrocytes. In contrast, NAC restored GPx1 expression in clasmatodendritic astrocytes and ameliorated this autophagic astroglial death. To the best of our knowledge, our findings report, for the first time, the spatiotemporal profiles of altered GPx1 expression in the rat hippocampus following SE, and suggest GSH-mediated GPx1 regulation, which may affect SE-induced neuronal death and autophagic astroglial degeneration.

Referemce:
Benzoxazole – Wikipedia,
Benzoxazole | C7H5NO – PubChem

Wang, Hui’s team published research in Small in 2022-03-03 | CAS: 83730-53-4

Oxygen-Deficient BiOCl Combined with L-Buthionine-Sulfoximine Synergistically Suppresses Tumor Growth through Enhanced Singlet Oxygen Generation under Ultrasound Irradiation. Recommended basis is Sulfoximine, Bioisosteric. Products is: https://www.ambeed.com/products/50578-18-2.html, 145026-07-9

Excess generation of reactive oxygen species (ROS) based on sensitizers under ultrasound (US) excitation can cause the death of tumor cells via oxidative damage, but sonosensitizers are largely unexplored. Herein, oxygen-deficient black BiOCl (B-BiOCl) nanoplates (NPs) are reported, with post-treatment on conventional BiOCl by simple UV excitation, showing stronger singlet oxygen (1O2) generation than com. TiO2 nanoparticles and their derivatives under US irradiation. Moreover, L-buthionine-sulfoximine (BSO), a GSH biosynthesis inhibitor, is incorporated into B-BiOCl NPs. The authors find that BSO can be released owing to the degradation of B-BiOCl NPs in the presence of acid and GSH, which are overexpressed in tumors. The results show that BSO/B-BiOCl-PEG NPs have a multifunctional synergistic effect on improving ROS production. In particular, BiOCl has remarkable near-IR light absorption after UV treatment and is good for photoacoustic imaging that can guide subsequent sonodynamic therapy. This work shows that just with a simple oxygen deficiency treatment, strong 1O2 generation can be provided to a conventional material under US irradiation and, interestingly, this effect can be amplified by using a small inhibitor BSO, and this is clearly demonstrated in cell and mice experiments

Referemce:
Benzoxazole – Wikipedia,
Benzoxazole | C7H5NO – PubChem

Cen, Yongjie’s team published research in Pesticide Biochemistry and Physiology in 2020-09-30 | CAS: 83730-53-4

Inhibition of the glutathione biosynthetic pathway increases phytochemical toxicity to Spodoptera litura and Nilaparvata lugens. Recommended basis is Sulfoximine, Bioisosteric. Products is: https://www.ambeed.com/products/50578-18-2.html, 145026-07-9

Phytochems. are toxic to insects, but their insecticidal efficiencies are usually low compared to synthetic insecticides. Understanding the mechanism of insect adaptation to phytochems. will provide guidance for increasing their efficacy. We found that exposure to 0.5% indole-3-methanol (I3C), xanthotoxin, and rotenone (ROT) significantly retarded the growth of Spodoptera litura larvae. The oxidative stress in S. litura larvae exposed to phytochems. was increased. The up-regulation of glutamate cysteine ligase but not glutathione reductase revealed that the de novo synthesis pathway is responsible for GSH synthesis in phytochem.-treated larvae. Treatment with the inhibitor (BSO) of ¦Ã-glutamylcysteine synthetase (gclc), a subunit of glutamate cysteine ligase, resulted in decreases of GSH levels and GST activities, increases of ROS levels in I3C-treated larvae, which finally caused midgut necrosis and larval death. Treatment with BSO or I3C alone did not cause larval death. The addition of GSH could partly reduce the influence of I3C and BSO on S. litura growth. Nilaparvata lugens gclc RNAi confirmed the result of BSO treatment in S. litura. N. lugens gclc RNAi significantly increased the mortality of ROT-sprayed N. lugens, in which ROS levels were significantly increased. All data indicate that gclc is involved in insect response to phytochem. treatment. Treatment with dsgclc will increase the insecticidal efficacy of plant-derived compounds

Referemce:
Benzoxazole – Wikipedia,
Benzoxazole | C7H5NO – PubChem

Porcher, Alexis’s team published research in Annals of Botany (Oxford, United Kingdom) in 2020 | CAS: 83730-53-4

Ascorbate glutathione-dependent H2O2 scavenging is an important process in axillary bud outgrowth in rosebush. Recommended basis is Sulfoximine, Bioisosteric. Products is: https://www.ambeed.com/products/50578-18-2.html, 145026-07-9

Branching is an important mechanism of plant shape establishment and the direct consequence of axillary bud outgrowth. Recently, hydrogen peroxide (H2O2) metabolism, known to be involved in plant growth and development, has been proposed to contribute to axillary bud outgrowth. However, the involvement of H2O2 in this process remains unclear. ? Methods We analyzed the content of H2O2 during bud outgrowth and characterized its catabolism, both at the transcriptional level and in terms of its enzymic activities, using RT-qPCR and spectrophotometric methods, resp. In addition, we used in vitro culture to characterize the effects of H2O2 application and the reduced glutathione (GSH) synthesis inhibitor L-buthionine sulfoximine (BSO) on bud outgrowth in relation to known mol. markers involved in this process. ? Key Results Quiescent buds displayed a high content of H2O2 that declined when bud outgrowth was initiated, as the consequence of an increase in the scavenging activity that is associated with glutathione pathways (ascorbate-glutathione cycle and glutathione biosynthesis); catalase did not appear to be implicated. Modification of bud redox state after the application of H2O2 or BSO prevented axillary bud outgrowth by repressing organogenesis and newly formed axis elongation. Hydrogen peroxide also repressed bud outgrowth-associated marker gene expression. ? Conclusions These results show that high levels of H2O2 in buds that are in a quiescent state prevents bud outgrowth. Induction of ascorbate-glutathione pathway scavenging activities results in a strong decrease in H2O2 content in buds, which finally allows bud outgrowth.

Referemce:
Benzoxazole – Wikipedia,
Benzoxazole | C7H5NO – PubChem

He, Canxia’s team published research in Molecules in 2021 | CAS: 83730-53-4

The Inhibitory Effect of Sulforaphane on Bladder Cancer Cell Depends on GSH Depletion-Induced by Nrf2 Translocation. Recommended basis is Sulfoximine, Bioisosteric. Products is: https://www.ambeed.com/products/50578-18-2.html, 145026-07-9

Sulforaphane (SFN), an isothiocyanate (ITCs) derived from glucosinolate that is found in cruciferous vegetables, has been reported to exert a promising anticancer effect in a substantial amount of scientific research. However, epidemical studies showed inconsistencies between cruciferous vegetable intake and bladder cancer risk. In this study, human bladder cancer T24 cells were used as in vitro model for revealing the inhibitory effect and its potential mechanism of SFN on cell growth. Here, a low dose of SFN (2.5 ¦ÌM) was shown to promote cell proliferation (5.18-11.84%) and migration in T24 cells, while high doses of SFN (>10 ¦ÌM) inhibited cell growth significantly. The induction effect of SFN on nuclear factor (erythroid-derived 2)-like 2 (Nrf2) expression at both low (2.5 ¦ÌM) and high dose (10 ¦ÌM) was characterized by a bell-shaped curve. Nrf2 and glutathione (GSH) might be the underlying mechanism in the effect of SFN on T24 cell growth since Nrf2 siRNA and GSH-depleting agent L-Buthionine-sulfoximine abolished the effect of SFN on cell proliferation. In summary, the inhibitory effect of SFN on bladder cancer cell growth and migration is highly dependent on Nrf2-mediated GSH depletion and following production These findings suggested that a higher dose of SFN is required for the prevention and treatment of bladder cancer.

Referemce:
Benzoxazole – Wikipedia,
Benzoxazole | C7H5NO – PubChem

Ramazani, Yasaman’s team published research in PLoS One in 2021 | CAS: 83730-53-4

Therapeutic concentrations of calcineurin inhibitors do not deregulate glutathione redox balance in human renal proximal tubule cells. Recommended basis is Sulfoximine, Bioisosteric. Products is: https://www.ambeed.com/products/50578-18-2.html, 145026-07-9

The calcineurin inhibitors (CNI) cyclosporine A and tacrolimus comprise the basis of immunosuppressive regimes in all solid organ transplantation. However, long-term or high exposure to CNI leads to histol. and functional renal damage (CNI-associated nephrotoxicity). In the kidney, proximal tubule cells are the only cells that metabolize CNI and these cells are believed to play a central role in the origin of the toxicity for this class of drugs, although the underlying mechanisms are not clear. Several studies have reported oxidative stress as an important mediator of CNI-associated nephrotoxicity in response to CNI exposure in different available proximal tubule cell models. However, former models often made use of supra-therapeutic levels of tissue drug exposure. In addition, they were not shown to express the relevant enzymes (e.g., CYP3A5) and transporters (e.g., P-glycoprotein) for the metabolism of CNI in human proximal tubule cells. Moreover, the used methods for detecting ROS were potentially prone to false pos. results. In this study, we used a novel proximal tubule cell model established from human allograft biopsies that demonstrated functional expression of relevant enzymes and transporters for the disposition of CNI. We exposed these cells to CNI concentrations as found in tissue of stable solid organ transplant recipients with therapeutic blood concentrations We measured the glutathione redox balance in this cell model by using organelle-targeted variants of roGFP2, a highly sensitive green fluorescent reporter protein that dynamically equilibrates with the glutathione redox couple through the action of endogenous glutaredoxins. Our findings provide evidence that CNI, at concentrations commonly found in allograft biopsies, do not alter the glutathione redox balance in mitochondria, peroxisomes, and the cytosol. However, at supra-therapeutic concentrations, cyclosporine A but not tacrolimus increases the ratio of oxidized/reduced glutathione in the mitochondria, suggestive of imbalances in the redox environment.

Referemce:
Benzoxazole – Wikipedia,
Benzoxazole | C7H5NO – PubChem

Liu, Wenjing’s team published research in Chemosphere in 2021-09-30 | CAS: 83730-53-4

Heat shock induces cross adaptation to aluminum stress through enhancing ascorbate-glutathione cycle in wheat seedlings. Recommended basis is Sulfoximine, Bioisosteric. Products is: https://www.ambeed.com/products/50578-18-2.html, 145026-07-9

Aluminum (Al), a neurotoxin agent, is universal in the earth crust, but its bioavailability and toxicity are manifested under acidic conditions. Up to 60% of the acid soils are distributed in tropical and subtropical regions, where crops simultaneously experience heat-shock stress. Here, we investigated the effects of heat shock-priming on Al tolerance in two different wheat genotypes. Conditioning of wheat seedlings with short period high temperature significantly alleviated Al-induced root growth inhibition, but did not significantly affect Al accumulation. However, we observed that heat shock-primed roots maintained lower levels of lipid peroxidation and higher cell viability. These priming-triggered effects were associated with reactive oxygen species (ROS) homeostasis. Furthermore, conditioning of plants with high temperature increased the contents of reduced ascorbate and glutathione, and ratios of reduced to oxidized forms of these mols. in wheat roots. However, ascorbate or glutathione biosynthesis inhibitors markedly prevented heat shock priming-induced ROS reduction accompanied by aggravated root elongation. Moreover, heat shock-priming enhanced the metabolic intensity of ascorbate-glutathione cycle, as activities of the cycle-allied enzymes were significantly increased. These results suggest that heat-shock induces cross adaptation to Al toxicity through sustaining efficient ascorbate-glutathione cycle operation in wheat plants.

Referemce:
Benzoxazole – Wikipedia,
Benzoxazole | C7H5NO – PubChem