Month: December 2022

Xu, Qingbo published the artcileManganese porphyrin-based metal-organic framework for synergistic sonodynamic therapy and ferroptosis inhypoxic tumors, Category: esters-buliding-blocks, the main research area is manganese porphyrin metal organic framework sonodynamic therapy ferroptosis; GSH depletion; catalase-like activity; ferroptosis; metal-organic framework; reactive oxygen species; sonodynamic therapy.

Development of efficient therapeutic strategy to incorporate ultrasound (US)-triggered sonodynamic therapy (SDT) and ferroptosis is highly promising in cancer therapy. However, the SDT efficacy is severely limited by the hypoxia and high glutathione (GSH) in the tumor microenvironment, and ferroptosis is highly associated with reactive oxygen species (ROS) and GSH depletion. A manganese porphyrin-based metal-organic framework (Mn-MOF) was constructed as a nanosensitizer to self-supply oxygen (O2) and decrease GSH for enhanced SDT and ferroptosis. In vitro and in vivo anal., including characterization, O2 generation, GSH depletion, ROS generation, lipid peroxidation, antitumor efficacy and tumor immune microenvironment were systematically evaluated. Mn-MOF exhibited catalase-like and GSH decreasing activity in vitro. After efficient internalization into cancer cells, Mn-MOF persistently catalyzed tumor-overexpressed H2O2 to in-situ produce O2 to relieve tumor hypoxia and decrease GSH and GPX4, which facilitated the formation of ROS and ferroptosis to kill cancer cells upon US irradiation in hypoxic tumors. Thus, strong anticancer and anti-metastatic activity was found in H22 and 4T1 tumor-bearing mice after a single administration of Mn-MOF upon a single US irradiation In addition, Mn-MOF showed strong antitumor immunity and improved immunosuppressive microenvironment upon US irradiation by increasing the numbers of activated CD8+ T cells and matured dendritic cells and decreaing the numbers of myeloid-derived suppressor cells in tumor tissues. Mn-MOF holds great potential for hypoxic cancer therapy.

Theranostics published new progress about Antitumor agents. 2044-85-1 belongs to class esters-buliding-blocks, name is 2′,7′-Dichloro-3-oxo-3H-spiro[isobenzofuran-1,9′-xanthene]-3′,6′-diyl diacetate, and the molecular formula is C24H14Cl2O7, Category: esters-buliding-blocks.

Referemce:
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

Kim, Ho Shin published the artcileImprovement of Oral Bioavailability of Pyrazolo-Pyridone Inhibitors of the Interaction of DCN1/2 and UBE2M, HPLC of Formula: 623-50-7, the main research area is carcinoma DCN1 UBE2M interaction inhibitors NEDD8 pharmacokinetic oral bioavailability.

The cullin-RING ubiquitin ligases (CRLs) are ubiquitin E3 enzymes that play a key role in controlling proteasomal degradation and are activated by neddylation. We previously reported inhibitors that target CRL activation by disrupting the interaction of defective in cullin neddylation 1 (DCN1), a CRL neddylation co-E3, and UBE2M, a neddylation E2. Our first-generation inhibitors possessed poor oral bioavailability and fairly rapid clearance that hindered the study of acute inhibition of DCN-controlled CRL activity in vivo. Herein, we report studies to improve the pharmacokinetic performance of the pyrazolo-pyridone inhibitors. The current best inhibitor, 40 (I), inhibits the interaction of DCN1 and UBE2M, blocks NEDD8 transfer in biochem. assays, thermally stabilizes cellular DCN1, and inhibits anchorage-independent growth in a DCN1 amplified squamous cell carcinoma cell line. Addnl., we demonstrate that a single oral 50 mg/kg dose sustains plasma exposures above the biochem. IC90 for 24 h in mice.

Journal of Medicinal Chemistry published new progress about Antitumor agents. 623-50-7 belongs to class esters-buliding-blocks, name is Ethyl 2-hydroxyacetate, and the molecular formula is C4H8O3, HPLC of Formula: 623-50-7.

Referemce:
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

Wang, Shupeng published the artcileTransmucosal Delivery of Self-Assembling Photosensitizer-Nitazoxanide Nanocomplexes with Fluorinated Chitosan for Instillation-Based Photodynamic Therapy of Orthotopic Bladder Tumors, Product Details of C12H9N3O5S, the main research area is photosensitizer nitazoxanide HSA chlorinee6 fluorinated chitosan bladder tumor PDT; bladder cancer; fluorinated chitosan; instillation-based photodynamic therapy; nitazoxanide; transmucosal delivery.

Theor., on account of improved local bioavailability of photosensitizers and attenuated systemic phototoxicity, intravesical instillation-based photodynamic therapy (PDT) for bladder cancer (BCa) would demonstrate significant advantages in comparison with the i.v. route. Actually, the low transmucosal efficiency, hypoxia regulation deficiency, as well as the biosafety risks of intravesical drug agents all have greatly limited the clin. development of instillation-based PDT for BCa. Herein, based on our recent findings on bladder intravesical vectors and photodynamic treatment, we explore and find that the conventional antiparasitic agent nitazoxanide (NTZ) by mixing with chlorine e6 (Ce6) conjugated human serum albumin (HSA), HSA-Ce6, is capable of forming self-assembled HSA-Ce6/NTZ nanoparticles (NPs). Then, the HSA-Ce6/NTZ complexes further fabricate with fluorinated chitosan (FCS), the synthesized transmucosal carrier, to form a biocompatible nanoscale system HSA-Ce6/NTZ/FCS NPs, which exhibit remarkably improved transmucosal delivery and uptake capacities compared with HSA-Ce6/NTZ alone or non-fluorinated HSA-Ce6/NTZ/CS NPs. Meanwhile, due to the metabolic regulation of tumor cells by NTZ, the tumor hypoxia could be efficaciously ameliorated to further favor PDT. This work represents a new photosensitizer nanomedicine formulation for the perfection of PDT performance through the modulation of tumor hypoxia by clin. approved agents. Thus, intravesical instillation of HSA-Ce6/NTZ/FCS NPs with favorable biocompatibility, followed by cystoscope-mediated PDT, could achieve a dramatically improved therapeutic effect to ablate orthotopic bladder tumors.

ACS Biomaterials Science & Engineering published new progress about Antitumor agents. 55981-09-4 belongs to class esters-buliding-blocks, name is 2-((5-Nitrothiazol-2-yl)carbamoyl)phenyl acetate, and the molecular formula is C12H9N3O5S, Product Details of C12H9N3O5S.

Referemce:
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

Kiehl, Isis G. A. published the artcileBoosting bladder cancer treatment by intravesical nitazoxanide and bacillus calmette-guerin association, Application In Synthesis of 55981-09-4, the main research area is bladder cancer intravesical nitazoxanide BCG; Bacillus calmette-guérin; Nitazoxanide; Repurposed drug; Treatment; Urinary bladder cancer.

Abstract: Purpose: Nitazoxanide (NTZ) has shown a promising antitumoral effect, the current study compared the anti-neoplastic effects of intravesical NTZ and BCG plus NTZ in NMIBC animal model. Methods: 30 rats, Fisher 344 were instilled with 4 intravesical doses of 1.5 mg/kg of N-methyl-N-nitrosourea (MNU) every 15 days for BC induction. The animals were divided into 3 groups (Group BCG 106 UFC -1 mg of BCG; Group NTZ -300 mg/kg of NTZ; Group NTZ + BCG -simultaneous treatment of BCG and NTZ) and received weekly intravesical treatment for 6 consecutive weeks. Animals were submitted to ultrasound imaging and euthanasia, their bladders were collected and histopathol., immunohistochem. tests (ki67 e c-Myc) and Western Blotting (PI3K, mTOR, and p-4E-BP) were performed. Results: Histopathol. tests showed 66.67%, 62.5% and 37.5% incidence of BC in animals treated with BCG, NTZ, and NTZ + BCG, resp. Nuclear positivity for ki-67 in BC animals were 12.4%, 13.2% and 8.8% in BCG, NTZ and NTZ + BCG group, resp. Between animals with carcinoma, c-Myc strong pos. was 40.10% in NTZ, 32.2% in BCG and 19.90% in the NTZ + BCG group. Blotting has shown mTOR (p =0.0473) and PI3K inhibition (p = 0.0349) in the presence of BCG, added to 4-EBP inhibition in the presence of NTZ. Conclusions: Results show the possible synergy between the gold standard BC treatment BCG and NTZ, in which multiple targets inhibition such as c-Myc and downstream mTOR, p-4E-BP and PI3K might play a role.

World Journal of Urology published new progress about Antitumor agents. 55981-09-4 belongs to class esters-buliding-blocks, name is 2-((5-Nitrothiazol-2-yl)carbamoyl)phenyl acetate, and the molecular formula is C12H9N3O5S, Application In Synthesis of 55981-09-4.

Referemce:
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

Stefanick, Jared F. published the artcileA Systematic Analysis of Peptide Linker Length and Liposomal Polyethylene Glycol Coating on Cellular Uptake of Peptide-Targeted Liposomes, Recommanded Product: 1-(9H-Fluoren-9-yl)-3-oxo-2,7,10,13,16,19-hexaoxa-4-azadocosan-22-oic acid, the main research area is peptide linker liposome polyethylene glycol coating cell uptake targeting.

PEGylated liposomes are attractive pharmaceutical nanocarriers; however, literature reports of ligand-targeted nanoparticles have not consistently shown successful results. Here, we employed a multifaceted synthetic strategy to prepare peptide-targeted liposomal nanoparticles with high purity, reproducibility, and precisely controlled stoichiometry of functionalities to evaluate the role of liposomal PEG coating, peptide EG-linker length, and peptide valency on cellular uptake in a systematic manner. We analyzed these parameters in two distinct disease models where the liposomes were functionalized with either HER2- or VLA-4-antagonistic peptides to target HER2-overexpressing breast cancer cells or VLA-4-overexpressing myeloma cells, resp. When targeting peptides were tethered to nanoparticles with an EG45 (∼PEG2000) linker in a manner similar to a more traditional formulation, their cellular uptake was not enhanced compared to non-targeted versions regardless of the liposomal PEG coating used. Conversely, reduction of the liposomal PEG to PEG350 and the peptide linker to EG12 dramatically enhanced cellular uptake by âˆ? fold and âˆ?00 fold in the breast cancer and multiple myeloma cells, resp. Uptake efficiency reached a maximum and a plateau with âˆ?% peptide d. in both disease models. Taken together, these results demonstrate the significance of using the right design elements such as the appropriate peptide EG-linker length in coordination with the appropriate liposomal PEG coating and optimal ligand d. in efficient cellular uptake of liposomal nanoparticles.

ACS Nano published new progress about Antitumor agents. 882847-32-7 belongs to class esters-buliding-blocks, name is 1-(9H-Fluoren-9-yl)-3-oxo-2,7,10,13,16,19-hexaoxa-4-azadocosan-22-oic acid, and the molecular formula is C28H37NO9, Recommanded Product: 1-(9H-Fluoren-9-yl)-3-oxo-2,7,10,13,16,19-hexaoxa-4-azadocosan-22-oic acid.

Referemce:
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

Li, Chao-Qing published the artcileIn situ synthesis of multifunctional tellurium nanorods stabilized by polypeptide-engineered for photothermal-sonodynamic combination therapy of tumors, Recommanded Product: 2′,7′-Dichloro-3-oxo-3H-spiro[isobenzofuran-1,9′-xanthene]-3′,6′-diyl diacetate, the main research area is breast cancer tellurium nanorods polypeptide photothermal sonodynamic combination therapy.

Nanoparticles containing elemental tellurium (Te) have been aroused extensive attention in biomedical applications. However, the ideal synthesis methods and effective anti-cancer strategies of Te nanoparticles remain great challenges. In this study, genetically engineered polypeptide (PC10ARGD)-capped Te nanorods (P-TeNRs) was in situ synthesized. The excellent dispersion of P-TeNRs with average lengths of 25.2 ± 4.65 nm and diameters of 6.5 ± 0.83 nm were confirmed by TEM. PC10ARGD was integrated onto the surface of Te nanorods to enhance the stability and biocompatibility of P-TeNRs. P-TeNRs exhibited the excellent photothermal conversion performance under irradiation of NIR laser and the reactive oxygen species (ROS) generating capacity under ultrasound (US) irradiation, which can achieve photothermal therapy and sonodynamic therapy of tumors. Compared with single photothermal therapy and sonodynamic therapy, the results of in vitro and in vivo experiments showed that the combination therapy has a synergistic effect on breast 4T1 tumors. In addition, the results of in vivo toxicity assay suggested that synthesized P-TeNRs presented negligible toxicity. These results demonstrate that this P-TeNRs can be engineered as a novel theranostic nanoplatform for synergistic photothermal-sonodynamic therapy of tumors.

Chemical Engineering Journal (Amsterdam, Netherlands) published new progress about Antitumor agents. 2044-85-1 belongs to class esters-buliding-blocks, name is 2′,7′-Dichloro-3-oxo-3H-spiro[isobenzofuran-1,9′-xanthene]-3′,6′-diyl diacetate, and the molecular formula is C24H14Cl2O7, Recommanded Product: 2′,7′-Dichloro-3-oxo-3H-spiro[isobenzofuran-1,9′-xanthene]-3′,6′-diyl diacetate.

Referemce:
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

Zhang, Xudong published the artcileAnticancer properties of different solvent extracts of Cucumis melo L. seeds and whole fruit and their metabolite profiling using HPLC and GC-MS, Application of Methyl docosanoate, the main research area is Cucumis seed fruit plant extract antitumor agent metabolite.

Honeydew melon (Cucumis melo L.) is an oval-shaped delicious fruit of one cultivar group of the muskmelon with immense nutritional importance and is extensively consumed by many tropical countries. The effect of various organic solvents on the recovery of phytochems. from honeydew melon plant fruits and seeds was assessed. Further, High-Performance Liquid Chromatog. (HPLC) was used to examine and assess the contents of phenolic acid (gallic acid) and flavonoid (rutin) compounds The use of gas chromatog.-mass spectrometry (GC-MS) anal. explained the presence of volatile phytocompounds in the extracts The use of organic solvents had a substantial impact on the total dry weight and extract yield. In general, the solvent-extracted constituents remained in the order of methanol>chloroform>distilled water for both honeydew melon seeds and whole fruit. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) was used to assess the cytotoxicity effect against PC3, HCT116, HeLa, and Jurkat cell lines. The chloroform extract exhibited a good cytotoxic activity against all cell lines as compared to other solvent extracts HPLC anal. revealed the occurrence of gallic acid content of 0.102±0.23 mg/10 mg of dry whole fruit extract, while 10 mg of dry seed extract contained only 0.022±0.12 mg of gallic acid content. Likewise, rutin content was observed to be 0.224±0.31 mg and 0.1916±0.82 mg/10 mg of dry whole fruit and seed extract, resp. Further, GC-MS anal. revealed the presence of a total of 37 compounds in chloroform extract of whole fruit, while only 14 compounds were found in seed extract Nevertheless, more examinations are needed to identify and characterize other metabolite from honeydew melon and evaluate their pharmacol. importance.

BioMed Research International published new progress about Antitumor agents. 929-77-1 belongs to class esters-buliding-blocks, name is Methyl docosanoate, and the molecular formula is C23H46O2, Application of Methyl docosanoate.

Referemce:
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

Knies, Christine published the artcileSynthesis of new potential lipophilic co-drugs of 2-Chloro-2′-deoxyadenosine (Cladribine, 2-CdA, Mavenclad, Leustatin) and 6-Azauridine (z6U) with valproic acid, Application In Synthesis of 539-88-8, the main research area is cladribine azauridine valproate synthesis lipophilic anticancer; biological activity; cancerostatic/cancerotoxic activity; cladribine; drug profiling; glioblastoma; multiple sclerosis; nucleolipids.

2-Chloro-2′-deoxyadenosine (cladribine, 1) was acylated with valproic acid (2) under various reaction conditions yielding 2-chloro-2′-deoxy-3′,5′-O-divalproyladenosine (3) as well as the 3′-O- and 5′-O-monovalproylated derivatives, 2-chloro-2′-deoxy-3′-O-valproyladenosine (4) and 2-chloro-2′-deoxy-5′-O-valproyladenosine (5), as new co-drugs. In addition, 6-azauridine-2′,3′-O-(Et levulinate) (8) was valproylated at the 5′-OH group (â†?). All products were characterized by 1H- and 13C-NMR spectroscopy and ESI mass spectrometry. The structure of the byproduct 6 (N-cyclohexyl-N-(cyclohexylcarbamoyl)-2-propylpentanamide), formed upon valproylation of cladribine in the presence of N,N-dimethylaminopyridine and dicyclohexylcarbodiimide, was analyzed by X-ray crystallog. Cladribine as well as its valproylated co-drugs were tested upon their cancerostatic/cancerotoxic activity in human astrocytoma/oligodendroglioma GOS-3 cells, in rat malignant neuro ectodermal BT4Ca cells, as well as in phorbol-12-myristate 13-acetate (PMA)-differentiated human THP-1 macrophages. The most important result of these experiments is the finding that only the 3′-O-valproylated derivative 4 exhibits a significant antitumor activity while the 5′-O- as well as the 3′,5′-O-divalproylated cladribine derivatives 3 and 5 proved to be inactive.

Chemistry & Biodiversity published new progress about Antitumor agents. 539-88-8 belongs to class esters-buliding-blocks, name is Ethyl 4-oxopentanoate, and the molecular formula is C7H12O3, Application In Synthesis of 539-88-8.

Referemce:
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

Hesami, Sadra published the artcileSynthesis and characterization of chitosan nanoparticles loaded with greater celandine (Chelidonium majus L.) essential oil as an anticancer agent on MCF-7 cell line, Safety of Benzyl acetate, the main research area is chitosan nanoparticle Chelidonium majus essential oil nticancer agent; Apoptosis; Breast cancer; Chelidonium majus L.; Chitosan nanoparticles; Encapsulation.

Essential oils (EOs) of greater celandine (GC) roots and leaves were extracted, and gas chromatog.-mass spectrometry (GC-MS) was used for analyzing them. Then they were loaded into chitosan nanoparticles (CNPs) using emulsion-ionic gelation method. CNPs loaded with greater celandine root essential oil (GCREO) and leave essential oil (GCLEO) were synthesized (size 76.5-115.3 nm) using an emulsion-ionic gelation method. Fourier Transform IR (FT-IR), spectroscopy, scanning electron microscope (SEM), and dynamic light scattering (DLS) were used for characterization of the formed NPs. Good encapsulation efficiency was confirmed for GCREO (62.5%) and GCLEO (69.1%) in CNPs. According to the MTT results, the synthesized NPs showed a dose-dependent effect on MCF-7 cell line. The inhibitory concentration (IC50) values for GCREO, GCLEO, CSNRs-GCREO and CNPs-GCLEO samples were 126.4, 90.2, 77.6, and 41.5 μg/mL, resp. The highest rate of apoptosis was obtained in the CNPs-GCLEO group (63.73%). The results revealed that the cytotoxicity of CSNRs-GCREO and CNPs-GCLEO against MCF-7 cell line was significantly higher than that of their free form, implying that encapsulation of GCREO and GCLEO in CNPs is an efficient technique for improving their anti-cancer activity against MCF-7 cell line.

International Journal of Biological Macromolecules published new progress about Antitumor agents. 140-11-4 belongs to class esters-buliding-blocks, name is Benzyl acetate, and the molecular formula is C9H10O2, Safety of Benzyl acetate.

Referemce:
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

Aggarwal, Monika published the artcileInhibition of helicase activity by a small molecule impairs Werner syndrome helicase (WRN) function in the cellular response to DNA damage or replication stress, Formula: C8H9NO4, the main research area is Werner syndrome helicase inhibitor NSC19630 topotecan synergism antitumor.

Modulation of DNA repair proteins by small mols. has attracted great interest. An in vitro helicase activity screen was used to identify mols. that modulate DNA unwinding by Werner syndrome helicase (WRN), mutated in the premature aging disorder Werner syndrome. A small mol. from the National Cancer Institute Diversity Set designated NSC 19630 [1-(propoxymethyl)-maleimide] was identified that inhibited WRN helicase activity but did not affect other DNA helicases [Bloom syndrome (BLM), Fanconi anemia group J (FANCJ), RECQ1, RecQ, UvrD, or DnaB]. Exposure of human cells to NSC 19630 dramatically impaired growth and proliferation, induced apoptosis in a WRN-dependent manner, and resulted in elevated γ-H2AX and proliferating cell nuclear antigen (PCNA) foci. NSC 19630 exposure led to delayed S-phase progression, consistent with the accumulation of stalled replication forks, and to DNA damage in a WRN-dependent manner. Exposure to NSC 19630 sensitized cancer cells to the G-quadruplex-binding compound telomestatin or a poly(ADP ribose) polymerase (PARP) inhibitor. Sublethal dosage of NSC 19630 and the chemotherapy drug topotecan acted synergistically to inhibit cell proliferation and induce DNA damage. The use of this WRN helicase inhibitor mol. may provide insight into the importance of WRN-mediated pathway(s) important for DNA repair and the replicational stress response.

Proceedings of the National Academy of Sciences of the United States of America published new progress about Antitumor agents. 72835-26-8 belongs to class esters-buliding-blocks, name is (2,5-Dioxo-2,5-dihydro-1H-pyrrol-1-yl)methyl propionate, and the molecular formula is C8H9NO4, Formula: C8H9NO4.

Referemce:
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics