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

Luo, Gang’s team published research in Yeast in 2021-11-30 | CAS: 83730-53-4

The mechanism of N-acetyl-L-cysteine in improving the secretion of porcine follicle-stimulating hormone in Pichia pastoris. 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.

Our previous study revealed that N-acetyl-L-cysteine (NAC) could enhance the secretion of recombinant proteins by Pichia pastoris, but the corresponding mol. mechanisms are still unclear. In the present study, we explored whether other thiols have a similar action on the secretion of recombinant human serum albumin and porcine FSH fusion protein (HSA-pFSH¦Â), to reveal the mechanism of NAC on HSA-pFSH¦Â secretion. Transcriptome anal. showed that genes involved in oxidoreductase activity and oxidation-reduction process were upregulated in cells supplemented with NAC. The other three thiol-reducing regents including dimercaptopropanol (DT), thioglycolic acid, and mercaptolactic acid could improve HSA-pFSH¦Â production in the culture supernatant. Among them, only DT had similar effect as NAC on HSA-pFSH¦Â secretion and the increase of GSH content. Moreover, 1-20 mM GSH, 1-10 mM cysteine, or 1-20 mM N-acetyl-D-cysteine supplementation could improve the secretion of HSA-pFSH¦Â. Furthermore, 0.4-3.2 mM ethacrynic acid, rather than 1-16 mM BSO could inhibit the effect of NAC on the production of HSA-pFSH¦Â. These results indicated that NAC improved the secretion of HSA-pFSH¦Â by increasing the intracellular GSH content through its thiol activity rather than as a precursor for GSH synthesis. In conclusion, our results demonstrate, for the first time, that the secretion of recombinant HSA-pFSH¦Â in Pichia pastoris could be improved through thiol-reducing agent supplementation, and the mechanism of the effect NAC has on HSA-pFSH¦Â secretion is associated with improving the intracellular GSH content.

Referemce:
Benzoxazole – Wikipedia,
Benzoxazole | C7H5NO – PubChem

Ta, Na’s team published research in Proceedings of the National Academy of Sciences of the United States of America in 2022-09-06 | CAS: 83730-53-4

Mitochondrial outer membrane protein FUNDC2 promotes ferroptosis and contributes to doxorubicin-induced cardiomyopathy. Recommended basis is Sulfoximine, Bioisosteric. Products is: https://www.ambeed.com/products/50578-18-2.html, 145026-07-9

Ferroptosis is an iron-dependent programmed necrosis characterized by glutathione (GSH) depletion and lipid peroxidation (LPO). Armed with both the pro- and antiferroptosis machineries, mitochondria play a central role in ferroptosis. However, how mitochondria sense the stress to activate ferroptosis under (patho-)physiol. settings remains incompletely understood. Here, we show that FUN14 domain-containing 2, also known as HCBP6 (FUNDC2), a highly conserved and ubiquitously expressed mitochondrial outer membrane protein, regulates ferroptosis and contributes to doxorubicin (DOX)-induced cardiomyopathy. We showed that knockout of FUNDC2 protected mice from DOX-induced cardiac injury by preventing ferroptosis. Mechanistic studies reveal that FUNDC2 interacts with SLC25A11, the mitochondrial glutathione transporter, to regulate mitoGSH levels. Specifically, knockdown of SLC25A11 in FUNDC2-knockout (KO) cells reduced mitoGSH and augmented erasin-induced ferroptosis. FUNDC2 also affected the stability of both SLC25A11 and glutathione peroxidase 4 (GPX4), key regulators for ferroptosis. Our results demonstrate that FUNDC2 modulates ferroptotic stress via regulating mitoGSH and further support a therapeutic strategy of cardioprotection by preventing mitoGSH depletion and ferroptosis.

Referemce:
Benzoxazole – Wikipedia,
Benzoxazole | C7H5NO – PubChem

Xiao, Shuting’s team published research in Chemical Engineering Journal (Amsterdam, Netherlands) in 2020-09-15 | CAS: 83730-53-4

Multifunctional FeS2 theranostic nanoparticles for photothermal-enhanced chemodynamic/photodynamic cancer therapy and photoacoustic imaging. Recommended basis is Sulfoximine, Bioisosteric. Products is: https://www.ambeed.com/products/50578-18-2.html, 145026-07-9

Chemodynamic therapy (CDT) and photodynamic therapy (PDT) mediated by reactive oxygen species (ROS) hold great potential for cancer therapy. However, they are still limited by rigorous reaction conditions of efficacious Fenton reaction, reliance on oxygen, and inherent defects of traditional common photosensitizers (PSs). Herein, we reported an L-Buthionine-sulfoximine (BSO) modified FeS2 nanoparticles (BSO-FeS2 NPs) with enhanced ROS generation under single wavelength (808 nm) laser irradiation First, FeS2 NPs showed high photothermal conversion efficiency (49.5%) and enhanced ¡¤O-2 and ¡¤OH generation capability via direct electron transfer presenting photothermal-improved Fenton reaction and photocatalytic ability. With the BSO modification, BSO-FeS2 NPs could inhibit the synthesis of glutathione (GSH) and accelerate the accumulation of ROS, which further enhanced the PDT/CDT treatment efficacy and resulted in high in vivo tumor inhibition rate (95%). Second, BSO-FeS2 NPs could activate the repolarization of macrophages from M2 to M1 for potential tumor immunotherapy. Last, BSO-FeS2 NPs showed good performance on photoacoustic imaging (PAI). All these results establish the capability of BSO-FeS2 NPs as nano-theranostic agents in PAI guided PTT/CDT/PDT combination therapy for cancer treatment.

Referemce:
Benzoxazole – Wikipedia,
Benzoxazole | C7H5NO – PubChem

Yildizhan, Kenan’s team published research in Molecular Neurobiology in 2020-08-31 | CAS: 83730-53-4

Glutathione Depletion and Parkinsonian Neurotoxin MPP+-Induced TRPM2 Channel Activation Play Central Roles in Oxidative Cytotoxicity and Inflammation in Microglia. Recommended basis is Sulfoximine, Bioisosteric. Products is: https://www.ambeed.com/products/50578-18-2.html, 145026-07-9

PD is one of most common neurodegenerative diseases. Environmental stressors such as oxidative stress (OS), calcium ion influx, apoptosis, and inflammation mechanisms are linked to activated microglia in patients with PD. The OS-dependent activated transient receptor potential melastatin 2 (TRPM2) channel is modulated in several neurons by glutathione (GSH). However, the cellular and mol. effects of GSH alteration on TRPM2 activation, OS, apoptosis, and inflammation in the microglia remain elusive. The microglia of TRPM2 wild-type (TRPM2-WT) and knockout (TRPM2-KO) mice were divided into control, PD model (MPP), L-buthionine sulfoximine (BSO), MPP + BSO and MPP + BSO + GSH groups. MPP-induced increases in apoptosis, death, OS, lipid peroxidation, PARP1, caspase-3 and caspase-9, inflammatory cytokines (IL-1beta, TNF-a, IL-6), and intracellular free Zn2+ and Ca2+ levels in the microglia of TRPM2-WT mice were further increased by the BSO treatment, although they were diminished by the GSH treatment. Their levels were further reduced by PARP1 inhibitors (PJ34 and DPQ) and TRPM2 blockers (ACA and 2-APB). However, the effects of MPP and BSO were not observed in the microglia of TRPM2-KO mice. Taken together, our data demonstrate that maintaining GSH homeostasis is not only important for quenching OS in the microglia of patients with PD but also equally critical to modulating TRPM2, thus suppressing inflammatory responses elicited by environmental stressors.

Referemce:
Benzoxazole – Wikipedia,
Benzoxazole | C7H5NO – PubChem

Wang, Mingshi’s team published research in iScience in 2022-09-16 | CAS: 83730-53-4

Selenium nanoparticle rapidly synthesized by a novel highly selenite-tolerant strain Proteus penneri LAB-1. Recommended basis is Sulfoximine, Bioisosteric. Products is: https://www.ambeed.com/products/50578-18-2.html, 145026-07-9

Microorganisms with high selenite-tolerant and efficient reduction ability of selenite have seldom been reported. In this study, a highly selenite-resistant strain (up to 500 mM), isolated from lateritic red soil, was identified as Proteus penneri LAB-1. Remarkably, isolate LAB-1 reduced nearly 2 mM of selenite within 18 h with the production of selenium nanoparticles (SeNPs) at the beginning of the exponential phase. Moreover, in vitro selenite reduction activities of strain LAB-1 were detected in the membrane protein fraction with or without NADPH/NADH as electron donors. Strain LAB-1 transported selenite to the membrane via nitrate transport protein. The selenite was reduced to SeNPs through the glutathione pathway and the catalysis of nitrate reductase, and the glutathione pathway played the decisive role. P. penneri LAB-1 could be a potential candidate for the selenite bioremediation and SeNPs synthesis.

Referemce:
Benzoxazole – Wikipedia,
Benzoxazole | C7H5NO – PubChem

Alamri, Saud’s team published research in Physiologia Plantarum in 2021-09-30 | CAS: 83730-53-4

Ascorbate and glutathione independently alleviate arsenate toxicity in brinjal but both require endogenous nitric oxide. Recommended basis is Sulfoximine, Bioisosteric. Products is: https://www.ambeed.com/products/50578-18-2.html, 145026-07-9

In this study, we have explored the possible role of ascorbic acid (ASC) and glutathione (GSH) in alleviating arsenate (AsV) toxicity in brinjal roots. Moreover, we have also focused our attention on the possible involvement of endogenous nitric oxide (NO) in accomplishing this task. AsV treatment neg. impacts the length and fresh weight of roots and shoots as well as the dry weight and fitness of roots, and this was accompanied by greater As accumulation in roots and shoots of brinjal. AsV treatment also declined the endogenous NO level by inhibiting Nitric Oxide Synthase-like (NOS-like) activity. Furthermore, AsV stimulated oxidative stress markers, caused protein damage by their carbonylation due to downregulation in antioxidants [particularly ascorbate (AsA)-GSH cycle], leading to disturbed cellular redox status. This, collectively, led to root cell death in brinjal. However, the addition of either ASC or GSH rescued brinjal roots from the toxic effects of AsV in. Interestingly, lycorine (an inhibitor of ASC biosynthesis) further increased AsV toxicity, while ASC rescued its effects. Moreover, buthionine sulfoximine (BSO, an inhibitor of GSH biosynthesis) interestingly increased further AsV toxicity, while GSH rescued the plant from the As toxic effects. An interesting notion of this study was that GSH rescued the toxic effect of lycorine, while ASC rescued the toxic effect of BSO, though the AsV toxicity mediated by either ASC or GSH was always accompanied by high endogenous NO level and NOS-like activity. All together, these results suggest that ASC and GSH independently mitigate AsV toxicity in brinjal roots, but both might be dependent on endogenous NO for accomplishing the AsV toxicity alleviatory tasks.

Referemce:
Benzoxazole – Wikipedia,
Benzoxazole | C7H5NO – PubChem

Luo, Yang’s team published research in Biomacromolecules in 2021-10-11 | CAS: 83730-53-4

pH-Sensitive Polymeric Vesicles for GOx/BSO Delivery and Synergetic Starvation-Ferroptosis Therapy of Tumor. Recommended basis is Sulfoximine, Bioisosteric. Products is: https://www.ambeed.com/products/50578-18-2.html, 145026-07-9

Typical glucose oxidase (GOx)-based starvation therapy is a promising strategy for tumor treatment; however, it is still difficult to achieve an effective therapeutic effect via a single starvation therapy. Herein, we designed a pH-sensitive polymeric vesicle (PV) self-assembled by histamine-modified chondroitin sulfate (CS-his) for codelivery of GOx and L-buthionine sulfoximine (BSO). GOx can consume glucose to induce the starvation therapy after the PVs reach cancer cell. Moreover, the product H2O2 will be reduced by a high concentration of glutathione (GSH) in the tumor cell, resulting in a reduction of the GSH content. The released BSO finally further reduced the GSH level. As a result, the signaling pathway of the ferroptosis will be activated. The in vivo results demonstrated that GOx/BSO@CS PVs exhibit a good inhibitory effect on the growth of 4T1 tumors in mice. Thus, this work provides a facile strategy to prepare pH-sensitive nanomedicine for synergistic starvation-ferroptosis therapy of tumor.

Referemce:
Benzoxazole – Wikipedia,
Benzoxazole | C7H5NO – PubChem

Feng, Ji’s team published research in Acta Pharmacologica Sinica in 2021-01-31 | CAS: 83730-53-4

ACSL4 is a predictive biomarker of sorafenib sensitivity in hepatocellular carcinoma. Recommended basis is Sulfoximine, Bioisosteric. Products is: https://www.ambeed.com/products/50578-18-2.html, 145026-07-9

Abstract: Sorafenib is the first-line treatment of advanced hepatocellular carcinoma (HCC). However, there is a lack of validated biomarkers to predict sorafenib sensitivity. In this study we investigated the role of ACSL4, a pos.-activating enzyme of ferroptosis, in sorafenib-induced cell death and HCC patient outcome. We showed that ACSL4 protein expression was neg. associated with IC50 values of sorafenib in a panel of HCC cell lines (R = -0.952, P < 0.001). Knockdown of ACSL4 expression by specific siRNA/sgRNA significantly attenuated sorafenib-induced lipid peroxidation and ferroptosis in Huh7 cells, and also rescued sorafenib-induced inhibition of xenograft tumor growth in vivo. We selected 29 HCC patients with surgery as primary treatment and sorafenib as postoperative adjunct therapy from a hospital-based cohort. A high proportion (66.7%) of HCC patients who had complete or partial responses to sorafenib treatment (according to the revised RECIST guideline) had higher ACSL4 expression in the pretreated HCC tissues, compared with those who had stable or progressed tumor growth (23.5%, P = 0.029). Since ACSL4 expression was independent of sorafenib treatment, it could serve as a useful predictive biomarker. Taken together, this study demonstrates that ACSL4 is essential for sorafenib-induced ferroptosis and useful for predicting sorafenib sensitivity in HCC. This study may have important translational impacts in precise treatment of HCC. ACSL4 is a predictive biomarker of sorafenib sensitivity in hepatocellular carcinoma. 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