83730-53-4 | Page 2 of 5 | Heterocyclic Building Blocks-Benzoxazole

Dong, Ziliang’s team published research in Chem in 2020-06-11 | CAS: 83730-53-4

Corrigendum: Synthesis of CaCO3-Based Nanomedicine for Enhanced Sonodynamic Therapy via Amplification of Tumor Oxidative Stress [Erratum to document cited in CA173:313754]. 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.

In the originally published version of this article, the confocal images of 4T1 cells from the PBS group in Figure 3C were unfortunately identical to those in the BSO group as a result of a copy-and-paste error during figure compilation. The corrections are provided.

Referemce:
Benzoxazole – Wikipedia,
Benzoxazole | C7H5NO – PubChem

Guan, Xin’s team published research in Advanced Functional Materials in 2020-07-06 | CAS: 83730-53-4

Tumor Metabolism-Engineered Composite Nanoplatforms Potentiate Sonodynamic Therapy via Reshaping Tumor Microenvironment and Facilitating Electron-Hole Pairs’ Separation. Recommended basis is Sulfoximine, Bioisosteric. Products is: https://www.ambeed.com/products/50578-18-2.html, 145026-07-9

Reactive oxygen species (ROS) depletion and low ROS production that result from the intratumoral redox metabolism equilibrium and low energy conversion efficiency from ultrasound mech. energy to ROS-represented chem. energy, resp., are two vital inhibitory factors of sonodynamic therapy (SDT). To address the two concerns, a tumor metabolism-engineered composite nanoplatform capable of intervening intratumoral ROS metabolism, breaking the redox equilibrium, and reshaping the tumor microenvironment is constructed to reinforce SDT against tumors. In this metabolism-engineered nanoplatform, Nb2C nanosheets serve as the scaffold to accommodate TiO2 sonosensitizers and L-buthionine-sulfoximine. Systematic experiments show that such nanoplatforms can reduce ROS depletion via suppressing glutathione synthesis and simultaneously improving ROS production via the Nb2C-enhanced production and separation of electron-hole pairs. Contributed by the combined effect, net ROS content can be significantly elevated, which results in the highly efficient anti-tumor outcomes in vivo and in vitro. Moreover, the combined design principles, i.e., tumor metabolism modulation for reducing ROS depletion and electron-hole pair separation for facilitating ROS production, can be extended to other ROS-dependent therapeutic systems.

Referemce:
Benzoxazole – Wikipedia,
Benzoxazole | C7H5NO – PubChem

Cadavid Vargas, J. F.’s team published research in JBIC, Journal of Biological Inorganic Chemistry in 2022-04-30 | CAS: 83730-53-4

Enhanced antitumor effect of L-buthionine sulfoximine or ionizing radiation by copper complexes with 2,2-biquinoline and sulfonamides on A549 2D and 3D lung cancer cell models. Recommended basis is Sulfoximine, Bioisosteric. Products is: https://www.ambeed.com/products/50578-18-2.html, 145026-07-9

Two ternary copper(II) complexes with 2,2-biquinoline (BQ) and with sulfonamides: sulfamethazine (SMT) or sulfaquinoxaline (SDQ) whose formulas are Cu(SMT)(BQ)Cl and Cu(SDQ)(BQ)Cl¡¤CH3OH, in what follows SMTCu and SDQCu, resp., induced oxidative stress by increasing ROS level from 1.0 ¦ÌM and the reduction potential of the couple GSSG/GSH2. The co-treatment with L-buthionine sulfoximine (BSO), which inhibits the production of GSH, enhanced the effect of copper complexes on tumor cell viability and on oxidative damage. Both complexes generated DNA strand breaks given by-at least partially-the oxidation of pyrimidine bases, which caused the arrest of the cell cycle in the G2/M phase. These phenomena triggered processes of apoptosis proven by activation of caspase 3 and externalization of phosphatidylserine and loss of cell integrity from 1.0 ¦ÌM. The combination with BSO induced a marked increase in the apoptotic population. On the other hand, an improved cell proliferation effect was observed when combining SDQCu with a radiation dose of 2 Gy from 1.0 ¦ÌM or with 6 Gy from 1.5 ¦ÌM. Finally, studies in multicellular spheroids demonstrated that even though copper(II) complexes did not inhibit cell invasion in collagen gels up to 48 h of treatment at the higher concentrations, multicellular resistance outperformed several drugs currently used in cancer treatment. Overall, our results reveal an antitumor effect of both complexes in monolayer and multicellular spheroids and an improvement with the addition of BSO. However, only SDQCu was the best adjuvant of ionizing radiation treatment.

Referemce:
Benzoxazole – Wikipedia,
Benzoxazole | C7H5NO – PubChem

Wu, Shengming’s team published research in Advanced Functional Materials in 2021-08-02 | CAS: 83730-53-4

GSH-Depleted Nanozymes with Dual-Radicals Enzyme Activities for Tumor Synergic Therapy. Recommended basis is Sulfoximine, Bioisosteric. Products is: https://www.ambeed.com/products/50578-18-2.html, 145026-07-9

Although inspiring progress has been achieved in tumor nanocatalytic therapies based on tailor-made nanozymes for converting hydrogen peroxide into reactive oxygen species (ROS) efficiently, most cytotoxic hydroxyl radicals do not spread far enough within a cell to damage the primary organelles for effective tumor therapy due to their short half-life time (?1¦Ìs). Developing a novel nanocatalyst platform involving longer half-life time ROS is desired. To this end, Fe3O4-Schwertmannite nanocomposites (Fe3O4-Sch) with triple-effect tumor therapy are constructed through a facile method. The Schwertmannite shell converts the ¡¤OH produced by Fe3O4 via the Fenton reaction into sulfate radicals with a longer half-life time (30¦Ìs). Combination of dual radicals exhibits overwhelming tumor inhibition efficacy. The nanocomposites also show the multifunctionality of good photothermal efficiency (33.2%) and synergistic oxidative stress amplification upon glutathione biosynthesis (GSH) depletion by the L-buthionine sulfoximine (BSO) mols. loaded in the hollow Fe3O4 cores. The comprehensive properties of the nanoplatform including the dual-radical production, Fe3O4 nanocrystal mediated PTT, and the BSO mediated GSH depletion result in remarkable tumor inhibition both in vitro and in vivo, which may pave a way to constructing a synergic catalytic nanoplatform for efficient tumor therapy.

Referemce:
Benzoxazole – Wikipedia,
Benzoxazole | C7H5NO – PubChem

Yoshioka, Hiromasa’s team published research in ACS Chemical Biology in 2022-02-18 | CAS: 83730-53-4

Identification of a Small Molecule That Enhances Ferroptosis via Inhibition of Ferroptosis Suppressor Protein 1 (FSP1). Recommended basis is Sulfoximine, Bioisosteric. Products is: https://www.ambeed.com/products/50578-18-2.html, 145026-07-9

Glutathione peroxidase 4 (GPX4) is an intracellular enzyme that oxidizes glutathione while reducing lipid peroxides, and is a promising target for cancer therapy. Till date, several GPX4 inhibitors have been reported to exhibit cytotoxicity against cancer cells. However, some cancer cells are less sensitive to the known GPX4 inhibitors. This study aimed to explore compounds showing synergistic effects with GPX4 inhibitors. We screened a chem. library and identified a compound named NPD4928 (I), whose cytotoxicity was enhanced in the presence of a GPX4 inhibitor. Furthermore, we identified ferroptosis suppressor protein 1 (FSP1) as its target protein. The results indicate that NPD4928 enhanced the sensitivity of various cancer cells to GPX4 inhibitors, suggesting the combination to possibly have therapeutic potential via the induction of ferroptosis.

Referemce:
Benzoxazole – Wikipedia,
Benzoxazole | C7H5NO – PubChem

Choi, Yeon Su’s team published research in Biomaterials in 2022-01-31 | CAS: 83730-53-4

Beyond hydrophilic polymers in amphiphilic polymer-based self-assembled NanoCarriers: Small hydrophilic carboxylate-capped disulfide drug delivery system and its multifunctionality and multispatial targetability. Recommended basis is Sulfoximine, Bioisosteric. Products is: https://www.ambeed.com/products/50578-18-2.html, 145026-07-9

Due to increasing safety and intracellular delivery concerns about hydrophilic polymers in amphiphilic polymer-based nanoparticles (NPs), this study investigates small hydrophilic mol.-stabilized NPs for effective intracellular delivery with multiorganelle targetability and dual responsiveness to acidic pH/glutathione (GSH). In the construction of small hydrophilic mol.-stabilized NP (MSPCL-NP), the A-B-A-type amphiphilic polymer (MSPCL-P) is composed of two short hydrophilic carboxylate-capped disulfide derivatives (A) that replace hydrophilic polymers and assist in providing colloidal stability and preventing antibody (e.g., at least anti-PEG antibody)-mediated specific interactions and complement activation in the plasma and a hydrophobic multiple disulfide-containing poly(¦Å-caprolactone) block (B) that carries hydrophobic drugs. The carboxylates on the surface of MSPCL-NP target the acidic extratumoral/endolysosomal milieu by sensing and buffering acidic pH values, and the hydrophobic carboxylic acids improve adsorptive endocytosis and effective endosomal escape. Multiple disulfide linkages selectively target cytosolic GSH, resulting in rapid drug release from the destroyed MSPCL-NP via the cleavage of disulfide bonds in MSPCL-P. Doxorubicin (DOX)-loaded NP (DOX@MSPCL-NP) exerts strong effects on killing cells in vitro and inhibits tumor growth in HCT116 xenograft tumor-bearing mice. In conclusion, the multifunctionality and multispatial targetability of MSPCL-NP might effectively overcome various sequential drug delivery hurdles, ranging from blood circulation to drug release. Furthermore, the introduction of small hydrophilic mols. represents a potential strategy to make self-assembled NPs without the use of hydrophilic polymers.

Referemce:
Benzoxazole – Wikipedia,
Benzoxazole | C7H5NO – PubChem

Gran, Evan Rizzel’s team published research in Nanomedicine (New York, NY, United States) in 2021-10-31 | CAS: 83730-53-4

Human astrocytes and astrocytoma respond differently to resveratrol. Recommended basis is Sulfoximine, Bioisosteric. Products is: https://www.ambeed.com/products/50578-18-2.html, 145026-07-9

A fundamental problem in oncol. is that anticancer chemotherapeutics kill both cancer and healthy cells in the surrounding tissues. Resveratrol is a natural antioxidant with intriguing and opposing biol. properties: it reduces viability of some cancer cells but not of non-transformed ones (in equimolar concentrations). Therefore, we examined resveratrol in human non-transformed primary astrocytes and astrocytoma. Resveratrol reduced reactive oxygen species in astrocytes, but not in astrocytoma. Such cell-type dependent response is particularly evident with analyses at the single cell level showing clear population difference in high and low glutathione levels. Due to resveratrol¡äs poor aqueous solubility that limits its use in clinics, we incorporated it into stimulus-responsive micelles assembled from miktoarm polymers. This could be an attractive chemotherapeutic delivery strategy in nano-oncol. As a proof of principle, we show that these formulations containing resveratrol markedly decrease astrocytoma viability, particularly in combination with temozolomide, a first line chemotherapeutic for astrocytoma.

Human astrocytes and astrocytoma respond differently to resveratrol. 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

Wan, Lihui’s team published research in Journal of Colloid and Interface Science in 2020-08-01 | CAS: 83730-53-4

A novel intratumoral pH/redox-dual-responsive nanoplatform for cancer MR imaging and therapy. Recommended basis is Sulfoximine, Bioisosteric. Products is: https://www.ambeed.com/products/50578-18-2.html, 145026-07-9

The integration of diagnostic and therapeutic functions in a nanoplatform has been a rapidly emerging method in the management of cancer. The application of imaging technol. paves the way to track the pharmacokinetics of the nanoplatforms, to guide the treatment, and to monitor the therapeutic processes and outcomes. Herein, we reported a novel type of monodisperses mesoporous silica-coated superparamagnetic iron oxide-based multifunctional nanoplatform (DOX@MMSN-SS-PEI-cit) for the diagnosis and treatment of cancer. The fabrication process included the surface modification of monodisperses mesoporous silica nanoparticle (MMSN) with branched polyethyleneimine (PEI) via disulfide bonds and the further coupling of citraconic anhydride to PEI. Typically, the hydrolysis of amide bonds in the tumor microenvironment (TME) could lead to a neg.-to-pos. charge reversion, which can enhance the endosomal escape of the resulting nanoplatform. The rapid release of doxorubicin hydrochloride (DOX) directly killed the cancer cells. Due to the superparamagnetic iron oxide-based high-resolution T2-weighted MR imaging contrast agents, this novel multifunctional nanoplatform successfully realized MR imaging, targeted drug delivery and controlled release in one system, and achieved significant improvement in tumor diagnosis and therapy. In summary, the therapeutic nanoplatform is a promising option in precise cancer treatment.

Referemce:
Benzoxazole – Wikipedia,
Benzoxazole | C7H5NO – PubChem

Zhang, Yuchen’s team published research in Nature Communications in 2021-12-31 | CAS: 83730-53-4

SARS-CoV-2 hijacks folate and one-carbon metabolism for viral replication. Recommended basis is Sulfoximine, Bioisosteric. Products is: https://www.ambeed.com/products/50578-18-2.html, 145026-07-9

The recently identified Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is the cause of the COVID-19 pandemic. How this novel beta-coronavirus virus, and coronaviruses more generally, alter cellular metabolism to support massive production of ?30 kB viral genomes and subgenomic viral RNAs remains largely unknown. To gain insights, transcriptional and metabolomic analyses are performed 8 h after SARS-CoV-2 infection, an early timepoint where the viral lifecycle is completed but prior to overt effects on host cell growth or survival. Here, we show that SARS-CoV-2 remodels host folate and one-carbon metabolism at the post-transcriptional level to support de novo purine synthesis, bypassing viral shutoff of host translation. Intracellular glucose and folate are depleted in SARS-CoV-2-infected cells, and viral replication is exquisitely sensitive to inhibitors of folate and one-carbon metabolism, notably methotrexate. Host metabolism targeted therapy could add to the armamentarium against future coronavirus outbreaks.

SARS-CoV-2 hijacks folate and one-carbon metabolism for viral replication. 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

Lin, Zhuoying’s team published research in Journal of Experimental & Clinical Cancer Research in 2021-12-31 | CAS: 83730-53-4

FOXC1 promotes HCC proliferation and metastasis by Upregulating DNMT3B to induce DNA Hypermethylation of CTH promoter. Recommended basis is Sulfoximine, Bioisosteric. Products is: https://www.ambeed.com/products/50578-18-2.html, 145026-07-9

Forkhead box C1 (FOXC1), as a member of the FOX family, is important for promote HCC invasion and metastasis. FOX family protein lays a pivotal role in metabolism ROS is involved in tumor progression and is associated with the expression of lots of transcription factors. We next explored the mechanism underlying FOXC1 modulating the metabolism and ROS hemostasis in HCC. We used amino acids arrays to verify which metabolism is involved in FOXC1-induced HCC. The kits were used to detect the ROS levels in HCC cells with over-expression or down-expression of FOXC1. After identified the downstream target genes and candidate pathway which regulated by FOXC1 during HCC progression in vitro and in vivo, we used western blot, immunohistochem., bisulfite genomic sequencing, methylation-specific PCR, chromatin immunoprecipitation anal. and luciferase reporter assays to explore the relationship of FOXC1 and downstream genes. Moreover, the correlation between FOXC1 and target genes and the correlation between target genes and the recurrence and overall survival were analyzed in two independent human HCC cohorts. Here, we reported that FOXC1 could inhibit the cysteine metabolism and increase reactive oxygen species (ROS) levels by regulating cysteine metabolism-related genes, cystathionine ¦Ã-lyase (CTH). Overexpression of CTH significantly suppressed FOXC1-induced HCC proliferation, invasion and metastasis, while the reduction in cell proliferation, invasion and metastasis caused by the inhibition of FOXC1 could be reversed by knockdown of CTH. Meanwhile, FOXC1 upregulated de novo DNA methylase 3B (DNMT3B) expression to induce DNA hypermethylation of CTH promoter, which resulted in low expression of CTH in HCC cells. Moreover, low levels of ROS induced by N-acetylcysteine (NAC) which is an antioxidant inhibited the cell proliferation, migration, and invasion abilities mediated by FOXC1 overexpression, whereas high levels of ROS induced by L-Buthionine-sulfoximine (BSO) rescued the suppression results mediated by FOXC1 knockdown. Our study demonstrated that the overexpression of FOXC1 that was induced by the ROS dependent on the extracellular regulated protein kinases 1 and 2 (ERK1/2)- phospho-ETS Transcription Factor 1 (p-ELK1) pathway. In human HCC tissues, FOXC1 expression was pos. correlated with oxidative damage marker 8-hydroxy-2′-deoxyguanosine (8-OHdG), p-ELK1 and DNMT3B expression, but neg. correlated with CTH expression. HCC patients with pos. co-expression of 8-OHdG/FOXC1 or p-ELK1/FOXC1 or FOXC1/DNMT3B had the worst prognosis, whereas HCC patients who had pos. FOXC1 and neg. CTH expression exhibited the worst prognosis. In a word, we clarify that the pos. feedback loop of ROS-FOXC1-cysteine metabolism-ROS is important for promoting liver cancer proliferation and metastasis, and this pathway may provide a prospective clin. treatment approach for HCC.

Referemce:
Benzoxazole – Wikipedia,
Benzoxazole | C7H5NO – PubChem