Month: October 2022

Gao, Yuan; Hai, Lina; Kang, Yuan; Qin, Wenjie; Liu, Fang; Cai, Runlan; Yang, Xiuwei; Qi, Yun published the artcile< Compound kushen injection induces immediate hypersensitivity reaction through promoting the production of platelet-activating factor via de novo pathway>, Computed Properties of 6882-68-4, the main research area is Sophora Smilacis root extract platelet activating factor hypersensitivity; compound kushen injection; de novo pathway of platelet-activating factor; matrine; non-immunologic immediate hypersensitivity reaction; platelet-activating factor.

Compound Kushen Injection (CKI) is a bis-herbal formulation extracted from Kushen (Radix Sophorae Flavescentis) and Baituling (Rhizoma Heterosmilacis Yunnanensis). Clin., it is used as the adjuvant treatment of cancer. However, with the increased application, the cases of immediate hypersensitivity reactions (IHRs) also gradually rise. In this study, we investigated the underlying mechanism(s) and active constituent(s) for CKI-induced IHRs in exptl. models. The obtained results showed that CKI did not elevate serum total IgE (tIgE) and mouse mast cell protease 1 (MMCP1) after consecutive immunization for 5 wk, but could induce Evans blue extravasation (local) and cause obvious hypothermia (systemic) after a single injection. Further study showed that alkaloids in Kushen, especially matrine, were responsible for CKI-induced IHRs. Mechanism study showed that various platelet-activating factor (PAF) receptor antagonists could significantly counter CKI-induced IHRs locally or systemically. In cell system, CKI was able to promote PAF production in a non-cell-selective manner. In cell lysate, the effect of CKI on PAF production became stronger and could be abolished by blocking de novo pathway. In conclusion, our study identifies, for the first time, that CKI is a PAF inducer. It causes non-immunol. IHRs, rather than IgE-dependent IHRs, by promoting PAF production through de novo pathway. Alkaloids in Kushen, especially matrine, are the prime culprits for IHRs. Our findings may provide a potential approach for preventing and treating CKI-induced IHRs.

Frontiers in Pharmacology published new progress about Alkaloids Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 6882-68-4 belongs to class naphthyridine, and the molecular formula is C15H24N2O, Computed Properties of 6882-68-4.

Referemce:
1,8-Naphthyridine – Wikipedia,
1,8-Naphthyridine | C8H6N2 – PubChem

Dai, Lin-Lin; Li, Dong-Dong; Zhao, Xiu-Mei; Zhi, Shuang; Shen, Hong-Sheng; Yang, Zi-Bo published the artcile< Synthesis and Antitumor Effect of Sophoridine Derivatives Bearing an Acyclic Aryloxy Phosphoramidate Mustard Functionality>, HPLC of Formula: 6882-68-4, the main research area is sophoridine aryloxy phosphoramidate mustard synthesis antitumor.

To elevate the potency of sophoridine, phosphoramidate mustard motif was incorporated to D-ring opened sophoridine scaffold. A series of acyclic aryloxy phosphoramidate mustard functionalized sophoridine derivatives were synthesized and screened for cytostatic activity in a range of different tumor cell lines (S180, H22, K562, MCF-7, SMMC-7721, and LoVo). All these compounds were shown to be more sensitive to S180 and H22 cells with IC50 values ranging from 2.10 to 7.21 μM. In addition, all targeted derivatives distinctly are more cytotoxic to cancer cells than normal cell L929. Compounds I (R = 3-ClC6H4, 4-BrC6H4, 1-naphthyl, 2-naphthyl) displayed moderate tumor suppression without apparent organ toxicity in vivo against mice bearing H22 liver tumors. Their potential binding modes with DNA topoisomerase I complex have also been investigated.

Journal of Heterocyclic Chemistry published new progress about Antitumor agents. 6882-68-4 belongs to class naphthyridine, and the molecular formula is C15H24N2O, HPLC of Formula: 6882-68-4.

Referemce:
1,8-Naphthyridine – Wikipedia,
1,8-Naphthyridine | C8H6N2 – PubChem

Kafita, Doris; Daka, Victor; Nkhoma, Panji; Zulu, Mildred; Zulu, Ephraim; Tembo, Rabecca; Ngwira, Zifa; Mwaba, Florence; Sinkala, Musalula; Munsaka, Sody published the artcile< High ELF4 expression in human cancers is associated with worse disease outcomes and increased resistance to anticancer drugs>, SDS of cas: 1223001-51-1, the main research area is transcription factor cancer resistance human anticancer drug.

The malignant phenotype of tumor cells is fuelled by changes in the expression of various transcription factors, including some of the well-studied proteins such as p53 and Myc. Despite significant progress made, little is known about several other transcription factors, including ELF4, and how they help shape the oncogenic processes in cancer cells. To this end, we performed a bioinformatics anal. to facilitate a detailed understanding of how the expression variations of ELF4 in human cancers are related to disease outcomes and the cancer cell drug responses. Here, using ELF4 mRNA expression data of 9,350 samples from the Cancer Genome Atlas pan-cancer project, we identify two groups of patient′s tumors: those that expressed high ELF4 transcripts and those that expressed low ELF4 transcripts across 32 different human cancers. We uncover that patients segregated into these two groups are associated with different clin. outcomes. Further, we find that tumors that express high ELF4 mRNA levels tend to be of a higher-grade, afflict a significantly older patient population and have a significantly higher mutation burden. By analyzing dose-response profiles to 397 anti-cancer drugs of 612 well-characterised human cancer cell lines, we discover that cell lines that expressed high ELF4 mRNA transcript are significantly less responsive to 129 anti-cancer drugs, and only significantly more response to three drugs: dasatinib, WH-4-023, and Ponatinib, all of which remarkably target the proto-oncogene tyrosine-protein kinase SRC and tyrosine-protein kinase ABL1. Collectively our analyses have shown that, across the 32 different human cancers, the patients afflicted with tumors that overexpress ELF4 tended to have a more aggressive disease that is also is more likely more refractory to most anti-cancer drugs, a finding upon which we could devise novel categorisation of patient tumors, treatment, and prognostic strategies.

PLoS One published new progress about Acute myeloid leukemia. 1223001-51-1 belongs to class naphthyridine, and the molecular formula is C24H15F3N4O, SDS of cas: 1223001-51-1.

Referemce:
1,8-Naphthyridine – Wikipedia,
1,8-Naphthyridine | C8H6N2 – PubChem

Bosch, Soraya S.; Lunev, Sergey; Batista, Fernando A.; Linzke, Marleen; Kronenberger, Thales; Domling, Alexander S. S.; Groves, Matthew R.; Wrenger, Carsten published the artcile< Molecular target validation of aspartate transcarbamoylase from Plasmodium falciparum by torin 2>, Reference of 1223001-51-1, the main research area is aspartate transcarbamoylase Plasmodium torin 2 drug target crystal structure; ATC; aspartate metabolism; drug target validation; malaria; protein interference assay; pyrimidine biosynthesis.

Malaria is a tropical disease that kills about half a million people around the world annually. Enzymic reactions within pyrimidine biosynthesis have been proven to be essential for Plasmodium proliferation. Here we report on the essentiality of the second enzymic step of the pyrimidine biosynthesis pathway, catalyzed by aspartate transcarbamoylase (ATC). Crystallization experiments using a double mutant of Plasmodium falciparum ATC (PfATC) revealed the importance of the mutated residues for enzyme catalysis. Subsequently, this mutant was employed in protein interference assays (PIAs), which resulted in inhibition of parasite proliferation when parasites transfected with the double mutant were cultivated in medium lacking an excess of nutrients, including aspartate. Addition of 5 or 10 mg/L of aspartate to the minimal medium restored the parasites’ normal growth rate. In vitro and whole-cell assays in the presence of the compound Torin 2 showed inhibition of specific activity and parasite growth, resp. In silico analyses revealed the potential binding mode of Torin 2 to PfATC. Furthermore, a transgenic ATC-overexpressing cell line exhibited a 10-fold increased tolerance to Torin 2 compared with control cultures. Taken together, our results confirm the antimalarial activity of Torin 2, suggesting PfATC as a target of this drug and a promising target for the development of novel antimalarials.

ACS Infectious Diseases published new progress about Antimalarials. 1223001-51-1 belongs to class naphthyridine, and the molecular formula is C24H15F3N4O, Reference of 1223001-51-1.

Referemce:
1,8-Naphthyridine – Wikipedia,
1,8-Naphthyridine | C8H6N2 – PubChem

Patidar, Khushboo; Panwar, Umesh; Vuree, Sugunakar; Sweta, Jajoriya; Sandhu, Manpreet Kaur; Nayarisseri, Anuraj; Singh, Sanjeev Kumar published the artcile< An in silico approach to identify high affinity small molecule targeting m-TOR inhibitors for the clinical treatment of breast cancer>, Category: naphthyridine, the main research area is breast cancer mTOR inhibitor sf1126 pharmacophore; Breast cancer; mTOR; Schrodinger Suite; Molecular Docking; MM-GBSA; virtual screening.

Breast cancer is the most frequent malignancy among women. It is a heterogeneous disease with different subtypes defined by its hormone receptor. A hormone receptor is mainly concerned with the progression of the PI3K/AKT/mTOR pathway which is often dysregulated in breast cancer. This is a major signaling pathway that controls the activities such as cell growth, cell division, and cell proliferation. The present study aims to suppress mTOR protein by its various inhibitors and to select one with the highest binding affinity to the receptor protein. Out of 40 inhibitors of mTOR against breast cancer, SF1126 was identified to have the best docking score of -8.705, using Schrodinger Suite which was further subjected for high throughput screening to obtain best similar compound using Lipinski’s filters. The compound obtained after virtual screening, ID: ZINC85569445 is seen to have the highest affinity with the target protein mTOR. The same result based on the binding free energy anal. using MM-GBSA showed that the compound ZINC85569445 to have the the highest binding free energy. The next study of interaction between the ligand and receptor protein with the pharmacophore mapping showed the best conjugates, and the ZINC85569445 can be further studied for future benefits of treatment of breast cancer.

Asian Pacific Journal of Cancer Prevention published new progress about Blood-brain barrier. 1223001-51-1 belongs to class naphthyridine, and the molecular formula is C24H15F3N4O, Category: naphthyridine.

Referemce:
1,8-Naphthyridine – Wikipedia,
1,8-Naphthyridine | C8H6N2 – PubChem

Lin, Bei-Bei; Liu, Xiang; Wu, San-Qiao; Zheng, Hong-Xing; Huo, Ke-Ke; Qi, Shan-Shan; Chen, Chen published the artcile< Phytochemicals content, antioxidant and antibacterial activities of Sophora viciifolia>, Name: (41S,7aR,13aR,13bR)-Dodecahydro-1H-dipyrido[2,1-f:3′,2′,1′-ij][1,6]naphthyridin-10(41H)-one, the main research area is phytochem antioxidant antibacterial Sophora extract; Sophora viciifolia; UPLC; antimicrobial activity; antioxidants; extract; phytochemistry.

The objective of this study is to compare the efficacy of ethanol extracts from different parts of Sophora viciifolia. The content of polyphenols, flavonoids, alkaloids, and antioxidant capacity, antimicrobial activity were investigated, and individual polyphenols and alkaloids were analyzed and quantified by ultra-high performance liquid chromatog. (UPLC). The microdilution method was used to determine the antimicrobial activity of extracts from S. viciifolia on six strains. The results for extracts from the different parts (flowers, leaves, and fruit) were compared in varying concentrations to determine whether one extract source is superior to another. Testing verified that extracts from the different parts of S. viciifolia did vary, as expected. For example, extract from the leaves had the best antimicrobial activity against pathogenic Candida albicans, but all extracts had good antimicrobial activity against the six tested strains. These results reveal that the active substances in S. viciifolia are abundant and have good antioxidant and antimicrobial activities, which can provide theor. support for the subsequent development and utilization of S. viciifolia extracts

Chemistry & Biodiversity published new progress about Alkaloids Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 6882-68-4 belongs to class naphthyridine, and the molecular formula is C15H24N2O, Name: (41S,7aR,13aR,13bR)-Dodecahydro-1H-dipyrido[2,1-f:3′,2′,1′-ij][1,6]naphthyridin-10(41H)-one.

Referemce:
1,8-Naphthyridine – Wikipedia,
1,8-Naphthyridine | C8H6N2 – PubChem

Wang, Rui; Liu, Hongwei; Shao, Yingying; Wang, Kailong; Yin, Shuangshuang; Qiu, Yuling; Wu, Honghua; Liu, Erwei; Wang, Tao; Gao, Xiumei; Yu, Haiyang published the artcile< Sophoridine inhibits human colorectal cancer progression via targeting MAPKAPK2>, Reference of 6882-68-4, the main research area is sophoridine MAPKAPK colorectal cancer progression human.

Radian Sophorae flavescentis is a traditional Chinese medicine commonly used to treat cancer in China. However, its active components and underlying mechanism remain ambiguous. In this study, we have screened the pharmacokinetic parameters of the main chem. constituents of Radian Sophorae flavescentis by Traditional Chinese Medicine Systems Pharmacol. (TCMSP) Database and Anal. Platform and have found that Sophoridine is one of the best antitumor active ingredients. We have found that MAPKAPK2 is a potential target for Sophoridine by the PharmMapper and KEGG databXase anal. Moreover, we have found that Sophoridine selectively inactivates phospho-MAPKAPK2 (Thr222) and directly binds into the ATP site of MAPKAPK2 by mol. docking. Furthermore, we have found out a direct binding between MAPKAPK2 and Sophoridine by cellular thermal shift assay and drug affinity responsive targets stability assay. The inhibition effects are further confirmed by Western blot: Sophoridine significantly decreases phospho-MAPKAPK2 (Thr222) in a time-dependent manner, but there is no obvious change in its total expression in colorectal cancer cells. Clin. studies have shown that a higher level of MAPKAPK2 is associated with a poorer percent survival rate (prognosis). Furthermore, a higher level of MAPKAPK2 is pos. associated with the enrichment of downregulation of apoptosis and autophagy by gene set enrichment anal., as well as upregulation of proliferation and cell-cycle arrest. Taken together, our results suggest that the MAPKAPK2 plays a key role in Sophoridine-inhibited growth and invasion in colorectal cancers.

Molecular Cancer Research published new progress about Animal gene Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 6882-68-4 belongs to class naphthyridine, and the molecular formula is C15H24N2O, Reference of 6882-68-4.

Referemce:
1,8-Naphthyridine – Wikipedia,
1,8-Naphthyridine | C8H6N2 – PubChem

Kumar, Sushil; Kumari, Renu; Pandey, Richa published the artcile< New insight-guided approaches to detect, cure, prevent and eliminate malaria>, Recommanded Product: 9-(6-Aminopyridin-3-yl)-1-(3-(trifluoromethyl)phenyl)benzo[h][1,6]naphthyridin-2(1H)-one, the main research area is review malaria diagnosis therapy prevention.

A review. New challenges posed by the development of resistance against artemisinin-based combination therapies (ACTs) as well as previous first-line therapies, and the continuing absence of vaccine, have given impetus to research in all areas of malaria control. This review portrays the ongoing progress in several directions of malaria research. The variants of RTS,S and apical membrane antigen 1 (AMA1) are being developed and test adapted as multicomponent and multistage malaria control vaccines, while many other vaccine candidates and methodologies to produce antigens are under experimentation. To track and prevent the spread of artemisinin resistance from Southeast Asia to other parts of the world, rolling circle-enhanced enzyme activity detection (REEAD), a time- and cost-effective malaria diagnosis in field conditions, and a DNA marker associated with artemisinin resistance have become available. Novel mosquito repellents and mosquito trapping and killing techniques much more effective than the prevalent ones are undergoing field testing. Mosquito lines stably infected with their symbiotic wild-type or genetically engineered bacteria that kill sympatric malaria parasites are being constructed and field tested for stopping malaria transmission. A complementary approach being pursued is the addition of ivermectin-like drug mols. to ACTs to cure malaria and kill mosquitoes. Experiments are in progress to eradicate malaria mosquito by making it genetically male sterile. High-throughput screening procedures are being developed and used to discover mols. that possess long in vivo half life and are active against liver and blood stages for the fast cure of malaria symptoms caused by simple or relapsing and drug-sensitive and drug-resistant types of varied malaria parasites, can stop gametocytogenesis and sporogony and could be given in one dose. Target-based antimalarial drug designing has begun. Some of the putative next-generation antimalarials that possess in their scaffold structure several of the desired properties of malaria cure and control are exemplified by OZ439, NITD609, ELQ300 and tafenoquine that are already undergoing clin. trials, and decoquinate, usnic acid, torin-2, ferroquine, WEHI-916, MMV396749 and benzothiophene-type N-myristoyltransferase (NMT) inhibitors, which are candidates for future clin. usage. Among these, NITD609, ELQ300, decoquinate, usnic acid, torin-2 and NMT inhibitors not only cure simple malaria and are prophylactic against simple malaria, but they also cure relapsing malaria.

Protoplasma published new progress about Antimalarials. 1223001-51-1 belongs to class naphthyridine, and the molecular formula is C24H15F3N4O, Recommanded Product: 9-(6-Aminopyridin-3-yl)-1-(3-(trifluoromethyl)phenyl)benzo[h][1,6]naphthyridin-2(1H)-one.

Referemce:
1,8-Naphthyridine – Wikipedia,
1,8-Naphthyridine | C8H6N2 – PubChem

Aung, T. N.; Nourmohammadi, S.; Qu, Z.; Harata-Lee, Y.; Cui, J.; Shen, H. Y.; Yool, A. J.; Pukala, T.; Du, Hong; Kortschak, R. D.; Wei, W.; Adelson, D. L. published the artcile< Fractional Deletion of Compound Kushen Injection Indicates Cytokine Signaling Pathways are Critical for its Perturbation of the Cell Cycle>, Product Details of C15H24N2O, the main research area is breast cancer cell cytokine signaling anticancer Kushen injection.

We used computational and exptl. biol. approaches to identify candidate mechanisms of action of aTraditional Chinese Medicine, Compound Kushen Injection (CKI), in a breast cancer cell line (MDA-MB-231). Because CKI is a complex mixture of plant secondary metabolites, we used a high-performance liquid chromatog. (HPLC) fractionation and reconstitution approach to define chem. fractions required for CKI to induce apoptosis. The initial fractionation separated major from minor compounds, and it showed that major compounds accounted for little of the activity of CKI. Furthermore, removal of no single major compound altered the effect of CKI on cell viability and apoptosis. However, simultaneous removal of two major compounds identified oxymatrine and oxysophocarpine as critical with respect to CKI activity. Transcriptome anal. was used to correlate compound removal with gene expression and phenotype data. Many compounds in CKI are required to trigger apoptosis but significant modulation of its activity is conferred by a small number of compounds In conclusion, CKI may be typical of many plant based extracts that contain many compounds in that no single compound is responsible for all of the bioactivity of the mixture and that many compounds interact in a complex fashion to influence a network containing many targets.

Scientific Reports published new progress about Adenocarcinoma. 6882-68-4 belongs to class naphthyridine, and the molecular formula is C15H24N2O, Product Details of C15H24N2O.

Referemce:
1,8-Naphthyridine – Wikipedia,
1,8-Naphthyridine | C8H6N2 – PubChem

Shalaby, Khaled; Mostafa, Ehab M.; Musa, Arafa; Moustafa, Abd El Ghany A.; Ibrahim, Mohamed F.; Alruwaili, Nabil K.; Zafar, Ameeduzzafar; Elmowafy, Mohammed published the artcile< Enhanced full-thickness wound healing via Sophora gibbosa extract delivery based on a chitosan/gelatin dressing incorporating microemulsion>, SDS of cas: 6882-68-4, the main research area is Sophora gibbosa extract chitosan gelatin wound healing dressing microemulsion; Sophora gibbosa; chitosan/gelatin; dressing; microemulsion; wound healing.

There are many synthetic drugs in literature have been utilized in healing of the wounds although the natural product specially antioxidants can offer similar if not better biol. activity in that regard. Genus Sophora is well known to contain flavonoids and phenolic compounds which have antioxidant and inflammatory effects. So, the aim of the current study was to develop and evaluate chitosan/gelatin based Sophora gibbosa extract-loaded microemulsion as wound dressing. Sophora gibbosa extract (SGE) contained 16 major compounds which have reasonable antioxidant activity. The developed microemulsion showed that Tween 80 produced significant (p < 0.05) lower particle size than Pluronic F127 at the same SGE concentration whereas high concentration of extract results in large particle size. Thermodn. stability studies showed that using higher concentration of the extract produced less stable formulations. The selected formulation was impregnated in the dressing base (chitosan/gelatin; 2:1 weight/weight ratio) which exhibited more water absorption. In vivo evaluation revealed that the dressing displayed superior wound repair compared to the control in terms histol. examination and determination of alpha smooth muscle actin (α-SMA) and proliferating cell nuclear antigen (PCNA). Thus, SGE-loaded microemulsion-impregnated gelatin/chitosan could be a potential candidate for the wound healing. Drug Development and Industrial Pharmacy published new progress about Absorption. 6882-68-4 belongs to class naphthyridine, and the molecular formula is C15H24N2O, SDS of cas: 6882-68-4.

Referemce:
1,8-Naphthyridine – Wikipedia,
1,8-Naphthyridine | C8H6N2 – PubChem