Category: naphthyridine

Cobbold, Simon A.; Chua, Hwa H.; Nijaga, Brunda; Creek, Darren J.; Ralph, Stuart A.; McConville, Malcolm J. published the artcile< Metabolic dysregulation induced in Plasmodium falciparum by dihydroartemisinin and other front-line antimalarial drugs>, Reference of 1223001-51-1, the main research area is Plasmodium dihydroartemisinin antimalarial metabolic dysregulation; Plasmodium; antimalarial; artemisinin; atovaquone; chloroquine; drug screening; malaria; metabolite; metabolomics; torin.

Detailed information on the mode of action of antimalarial drugs can be used to improve existing drugs, identify new drug targets, and understand the basis of drug resistance. In this study we describe the use of a time-resolved, mass spectrometry (MS)-based metabolite profiling approach to map the metabolic perturbations induced by a panel of clin. antimalarial drugs and inhibitors on Plasmodium falciparum asexual blood stages. Drug-induced changes in metabolite levels in P. falciparum-infected erythrocytes were monitored over time using gas chromatog.-MS and liquid chromatog.-MS and changes in specific metabolic fluxes confirmed by nonstationary [13C]-glucose labeling. Dihydroartemisinin (DHA) was found to disrupt Hb catabolism within 1 h of exposure, resulting in a transient decrease in Hb-derived peptides. Unexpectedly, it also disrupted pyrimidine biosynthesis, resulting in increased [13C]-glucose flux toward malate production, potentially explaining the susceptibility of P. falciparum to DHA during early blood-stage development. Unique metabolic signatures were also found for atovaquone, chloroquine, proguanil, cycloguanil and methylene blue. We also show that this approach can be used to identify the mode of action of novel antimalarials, such as the compound Torin 2, which inhibits Hb catabolism.

Journal of 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

Dong, Yaqian; Jia, Guoxiang; Hu, Jingwen; Liu, Hui; Wu, Tingting; Yang, Shenshen; Li, Yubo; Cai, Ting published the artcile< Determination of alkaloids and flavonoids in Sophora flavescens by UHPLC-Q-TOF/MS>, Reference of 6882-68-4, the main research area is Sophora flavescens alkaloid flavonoid determination UHPLC Q TOF MS.

This study is based on UHPLC-Q-TOF/MS and fragment ions to achieve classification and identification of alkaloids and flavonoids in Sophora flavescens. By reviewing the available and relevant literature, the mass fragmentation rules of alkaloids and flavonoids were summarized. 0.1% formic acid water (A) and acetonitrile (B) were used as mobile phases. 37 chem. constituents were identified, including 13 alkaloids and 24 flavonoids. This research method offers a complete strategy based on the fragmentation information of characteristic fragment ions and neutral loss obtained by MS/MS to characterize the chem. composition of Sophora flavescens.

Journal of Analytical Methods in Chemistry published new progress about Alkaloids Role: ANT (Analyte), ANST (Analytical 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

Liu, Yanlin; Duan, Xiaoli; Zhao, Xiaodi; Ding, Wenlong; Wang, Yaowei; Xiong, Yan published the artcile< Diverse nitrogen signals activate convergent ROP2-TOR signaling in Arabidopsis>, SDS of cas: 1223001-51-1, the main research area is diverse nitrogen signal ROP2TOR Arabidopsis; ROP2; TOR; amino acids; cell proliferation; inorganic nitrogen; leaf primordium.

The evolutionarily conserved target-of-rapamycin (TOR) kinase coordinates cellular and organismal growth in all eukaryotes. Amino acids (AAs) are key upstream signals for mammalian TOR activation, but how nitrogen-related nutrients regulate TOR signaling in plants is poorly understood. Here, we discovered that, independent of nitrogen assimilation, nitrate and ammonium function as primary nitrogen signals to activate TOR in the Arabidopsis leaf primordium. We further identified that a total of 15 proteinogenic AAs are also able to activate TOR, and the first AAs generated from plant specific nitrogen assimilation (glutamine), sulfur assimilation (cysteine), and glycolate cycle (glycine), exhibit the highest potency. Interestingly, nitrate, ammonium, and glutamine all activate the small GTPase Rho-related protein from plants 2 (ROP2), and constitutively active ROP2 restores TOR activation under nitrogen-starvation conditions. Our findings suggest that specific evolutionary adaptations of the nitrogen-TOR signaling pathway occurred in plant lineages, and ROP2 can integrate diverse nitrogen and hormone signals for plant TOR activation.

Developmental Cell published new progress about Amino acids Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 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

Krishnan, Karthik; Ziniel, Peter; Li, Hao; Huang, Xiuli; Hupalo, Daniel; Gombakomba, Nita; Guerrero, Sandra Mendoza; Dotrang, Thoai; Lu, Xiao; Caridha, Diana; Sternberg, Anna R.; Hughes, Emma; Sun, Wei; Bargieri, Daniel Y.; Roepe, Paul D.; Sciotti, Richard J.; Wilkerson, Matthew D.; Dalgard, Clifton L.; Tawa, Gregory J.; Wang, Amy Q.; Xu, Xin; Zheng, Wei; Sanderson, Philip E.; Huang, Wenwei; Williamson, Kim C. published the artcile< Torin 2 Derivative, NCATS-SM3710, Has Potent Multistage Antimalarial Activity through Inhibition of P. falciparum Phosphatidylinositol 4-Kinase (Pf PI4KIIIβ)>, Recommanded Product: 9-(6-Aminopyridin-3-yl)-1-(3-(trifluoromethyl)phenyl)benzo[h][1,6]naphthyridin-2(1H)-one, the main research area is plasmodium malaria drug discovery transmission blocking PI4K drug resistance.

Drug resistance is a constant threat to malaria control efforts making it important to maintain a good pipeline of new drug candidates. Of particular need are compounds that also block transmission by targeting sexual stage parasites. Mature sexual stages are relatively resistant to all currently used antimalarials except the 8-aminoquinolines that are not commonly used due to potential side effects. Here, we synthesized a new Torin 2 derivative, NCATS-SM3710(I) with increased aqueous solubility and specificity for Plasmodium and demonstrate potent in vivo activity against all P. berghei life cycle stages. NCATS-SM3710 also has low nanomolar EC50s against in vitro cultured asexual P. falciparum parasites (0.38 ± 0.04 nM) and late stage gametocytes (5.77 ± 1 nM). Two independent NCATS-SM3710/Torin 2 resistant P. falciparum parasite lines produced by growth in sublethal Torin 2 concentrations both had genetic changes in PF3D7_0509800, annotated as a phosphatidylinositol 4 kinase (Pf PI4KIIIβ). One line had a point mutation in the putative active site (V1357G), and the other line had a duplication of a locus containing Pf PI4KIIIβ. Both lines were also resistant to other Pf PI4K inhibitors. In addition NCATS-SM3710 inhibited purified Pf PI4KIIIβ with an IC50 of 2.0 ± 0.30 nM. Together the results demonstrate that Pf PI4KIIIβ is the target of Torin 2 and NCATS-SM3710 and provide new options for potent multistage drug development.

ACS Pharmacology & Translational Science published new progress about Drug mechanism of action. 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

Heinzen, Dennis; Dive, Iris; Lorenz, Nadja I.; Luger, Anna-Luisa; Steinbach, Joachim P.; Ronellenfitsch, Michael W. published the artcile< Second generation mTOR inhibitors as a double-edged sword in malignant glioma treatment>, Safety of 9-(6-Aminopyridin-3-yl)-1-(3-(trifluoromethyl)phenyl)benzo[h][1,6]naphthyridin-2(1H)-one, the main research area is mTOR inhibitor malignant glioma antitumor; glioblastoma; hypoxia; mTOR; mTOR inhibition; starvation; tumor microenvironment.

Glioblastomas (GBs) frequently display activation of the epidermal growth factor receptor (EGFR) and mammalian target of rapamycin (mTOR). mTOR exists as part of two multiprotein complexes, mTOR complex 1 (mTORC1) and 2 (mTORC2). In GBs, mTORC1 inhibitors such as rapamycin have performed poorly in clin. trials, and in vitro protect GB cells from nutrient and oxygen deprivation. Next generation ATP-competitive mTOR inhibitors with affinity for both mTOR complexes have been developed, but data exploring their effects on GB metabolism are scarce. In this study, we compared the ATP-competitive mTORC1/2 inhibitors torin2, INK-128 and NVP-Bez235 to the allostericmTORC1 inhibitor rapamycin under conditions that mimic the glioma microenvironment. In addition to inhibiting mTORC2 signaling, INK-128 and NVP-Bez235 more effectively blocked mTORC1 signaling and prompted a stronger cell growth inhibition, partly by inducing cell cycle arrest. However, under hypoxic and nutrient-poor conditions mTORC1/2 inhibitors displayed even stronger cytoprotective effects than rapamycin by reducing oxygen and glucose consumption. Thus, therapies that arrest proliferation and inhibit anabolic metabolism must be expected to improve energy homeostasis of tumor cells. These results mandate caution when treating physiol. or therapeutically induced hypoxic GBs with mTOR inhibitors.

International Journal of Molecular Sciences published new progress about Antitumor agents. 1223001-51-1 belongs to class naphthyridine, and the molecular formula is C24H15F3N4O, Safety of 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

Soliman, Ghada A.; Shukla, Surendra K.; Etekpo, Asserewou; Gunda, Venugopal; Steenson, Sharalyn M.; Gautam, Nagsen; Alnouti, Yazen; Singh, Pankaj K. published the artcile< The synergistic effect of an ATP-competitive inhibitor of mTOR and metformin on pancreatic tumor growth>, Application of C24H15F3N4O, the main research area is pancreatic tumor mTOR metformin.

We investigated the impact of inhibition of mTORC1/mTORC2 and synergism with metformin on pancreatic tumor growth and metabolomics. Cell lines derived from pancreatic tumors of the KPC (KrasG12D/+; p53R172H/+; Pdx1-Cre) transgenic mice model were implanted into the pancreas of C57BL/6 albino mice (n = 10/group). Two weeks later, the mice were injected i.p. with daily doses of 1) Torin 2 (mTORC1/mTORC2 inhibitor) at a high concentration (TH), 2) Torin 2 at a low concentration (TL), 3) metformin at a low concentration (ML), 4) a combination of Torin 2 and metformin at low concentrations (TLML), or 5) DMSO vehicle (control) for 12 d. Tissues and blood samples were collected for targeted xenometabolomics anal., drug concentration, and cell signaling. Metabolomic anal. of the control and treated plasma samples showed differential metabolite profiles. Phenylalanine was significantly elevated in the TLML group compared with the control (+426%, P = 0.0004), whereas uracil was significantly lower (-38%, P = 0.009). The combination treatment reduced tumor growth in the orthotopic mouse model. TLML significantly decreased tumor weights (0.66 ± 0.08 g; 52%) compared with the control (1.28 ± 0.19 g; 100%) (P < 0.002). The combination of mTOR dual inhibition by Torin 2 and metformin is associated with an altered metabolomic profile and a significant reduction in pancreatic tumor burden compared with single-agent therapy, and it is better tolerated. Current Developments in Nutrition published new progress about Pancreatic neoplasm. 1223001-51-1 belongs to class naphthyridine, and the molecular formula is C24H15F3N4O, Application of C24H15F3N4O.

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

Peng, Zhiyang; Guan, Qing; Luo, Jianfei; Deng, Wenhong; Liu, Jiasheng; Yan, Ruicheng; Wang, Weixing published the artcile< Sophoridine exerts tumor-suppressive activities via promoting ESRRG-mediated β-catenin degradation in gastric cancer>, 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 sophoridine tumor suppressive activity ESRRG catenin degradation gastric cancer; ESRRG; Gastric cancer; Sophoridine; β-Catenin.

As a natural alkaloid product isolated from Sophora alopecuroides. L, Sophoridine reshapes gastric cancer immune microenvironment via inhibiting chemotaxis and M2 polarization of tumor-associated macrophages (TAMs). However, the exact effects and underlying mechanism of Sophoridine on gastric cancer cells remains poorly known. The potential anti-tumor effects of Sophoridine on gastric cancer cell lines, including AGS and SGC7901 cells, were detected by CCK-8, EDU and colony forming assay, immunofluorescence, transwell assay, and flow cytometry. Mol. mechanisms of Sophoridine were investigated by siRNA transfection, nuclear/cytoplasmic extraction and western blot. The synergistic effects of Sophoridine with cisplatin on gastric cancer cells were further investigated in in vitro functional studies. Sophoridine exhibited potent tumor-suppressive activities in gastric cancer cells, including inhibition of proliferation, colony formulation, migration and invasion, as well as induction of apoptosis. In addition, we further showed that Sophoridine induced G2/M cell cycle arrest via inhibiting double-stranded DNA breaks repair and enhanced the efficacy of cisplatin in gastric cancer cells. Mol. studies further revealed that Sophoridine promoted β-catenin degradation by enhancing Estrogen-related receptor gamma (ESRRG) expression, but not depended on ubiquitination-proteasome pathway, either TRIM33-mediated (GSK3β-independent) or altered GSK3β activity, and thus exerted potent tumor-suppressive activities. Sophoridine depends on targeting ESRRG/β-catenin pathway to exert tumor-suppressive activities in gastric cancer cells and enhances the anti-tumor effect of cisplatin. Our study provided the promising preclin. anti-tumor evidence for the potential application of Sophoridine against gastric cancer.

BMC Cancer published new progress about Animal gene, Bcl-2 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

Yu, Pan; Cao, Weiya; Yang, Shilong; Wang, Yuan; Xia, Aixin; Tan, Xinlan; Wang, Luyi published the artcile< Design, synthesis and antitumor evaluation of novel quinazoline analogs in hepatocellular carcinoma cell>, Formula: C24H15F3N4O, the main research area is quinazoline preparation antitumor activity mol docking protein kinase inhibitor.

In this paper, five quinazoline analogs I (R = Cl, 1H-indol-5-yl, 4-chlorophenyl, pyridin-3-yl, 4-aminophenyl) were preliminary designed through scaffold shopping from mTOR inhibitors and synthesized in four steps. Five compounds I exhibited potent antitumor activity against the HepG2 cell line by MTT assay. Compound I (R = 1H-indol-5-yl) (II) (IC50 = 4.06μM) was found as the most potent analog and showed better antiproliferative ability than sorafenib (IC50 = 6.14μM). The result of the wound healing assay and transwell migration assay indicated II strong potential to suppress HepG2 cell migration in a dose- and time-dependent manner. The underlying mechanism of its cytotoxicity was also investigated and the results of western blotting confirmed that compound II exposure could block the cell cycle, promote apoptosis and inhibit AKT and mTOR phosphorylation in HepG2 cells. Mol. docking further supported that compound II showed a high affinity to mTOR kinase. The results favored rational design intention and hinted that the new quinazolines I might be helpful in the further explorations of potent agents.

Journal of Molecular Structure published new progress about Antitumor agents. 1223001-51-1 belongs to class naphthyridine, and the molecular formula is C24H15F3N4O, Formula: C24H15F3N4O.

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

Wang, Zhihan; Guo, Kai; Gao, Pan; Pu, Qinqin; Lin, Ping; Qin, Shugang; Xie, Na; Hur, Junguk; Li, Changlong; Huang, Canhua; Wu, Min published the artcile< Microbial and genetic-based framework identifies drug targets in inflammatory bowel disease>, Name: 9-(6-Aminopyridin-3-yl)-1-(3-(trifluoromethyl)phenyl)benzo[h][1,6]naphthyridin-2(1H)-one, the main research area is inflammatory bowel disease drug target microbial genetic framework; Inflammatory bowel disease; brefeldin-a; cyclic GMP-AMP synthase (cGAS); drug repurposing; host transcriptome-microbiome interaction.

With increasing incidence and prevalence of inflammatory bowel disease (IBD), it has become one of the major public health threats, and there is an urgent need to develop new therapeutic agents. Although the pathogenesis of IBD is still unclear, previous research has provided evidence for complex interplays between genetic, immune, microbial, and environmental factors. Here, we constructed a gene-microbiota interaction-based framework to discover IBD biomarkers and therapeutics. We identified candidate biomarkers for IBD by analyzing the publicly available transcriptomic and microbiome data from IBD cohorts. Animal models of IBD and diarrhea were established. The inflammation-correlated microbial and genetic variants in gene knockout mice were identified by 16S rRNA sequences and PCR array. We performed bioinformatic anal. of microbiome functional prediction and drug repurposing. Our validation experiments with cells and animals confirmed anti-inflammatory properties of a drug candidate. We identified the DNA-sensing enzyme cyclic GMP-AMP synthase (cGAS) as a potential biomarker for IBD in both patients and murine models. cGAS knockout mice were less susceptible to DSS-induced colitis. cGAS-associated gut microbiota and host genetic factors relating to IBD pathogenesis were also identified. Using a computational drug repurposing approach, we predicted 43 candidate drugs with high potency to reverse colitis-associated gene expression and validated that brefeldin-a mitigates inflammatory response in colitis mouse model and colon cancer cell lines. By integrating computational screening, microbiota interference, gene knockout techniques, and in vitro and in vivo validation, we built a framework for predicting biomarkers and host-microbe interaction targets and identifying repurposing drugs for IBD, which may be tested further for clin. application. This approach may also be a tool for repurposing drugs for treating other diseases.

Theranostics published new progress about Acetobacterium. 1223001-51-1 belongs to class naphthyridine, and the molecular formula is C24H15F3N4O, Name: 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

Zhu, Naiqiang; Hou, Jingyi published the artcile< Molecular mechanism of the anti-inflammatory effects of Sophorae Flavescentis Aiton identified by network pharmacology>, Quality Control of 6882-68-4, the main research area is Sophora flavescens antiinflammatory effect mol mechanism network pharmacol.

Inflammation, a protective response against infection and injury, involves a variety of biol. processes. Sophorae Flavescentis (Kushen) is a promising Traditional Chinese Medicine (TCM) for treating inflammation, but the pharmacol. mechanism of Kushen’s anti-inflammatory effect has not been fully elucidated. The bioactive compounds, predicted targets, and inflammation-related targets of Kushen were obtained from open source databases. The ”Component-Target” network and protein-protein interaction (PPI) network were constructed, and hub genes were screened out by topol. anal. Gene ontol. (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed on genes in the PPI network. Furthermore, nitric oxide (NO) production anal., RT-PCR, and western blot were performed to detect the mRNA and protein expression of hub genes in LPS-induced RAW264.7 cells. An immunofluorescence assay found that NF-κB p65 is translocated. A total of 24 bioactive compounds, 465 predicted targets, and 433 inflammation-related targets were identified and used to construct ”Component-Targets” and PPI networks. Then, the five hub genes with the highest values-IL-6, IL-1β, VEGFA, TNF-α, and PTGS2 (COX-2)- were screened out. Enrichment anal. results suggested mainly involved in the NF-κB signaling pathway. Moreover, experiments were performed to verify the predicted results. Kushen may mediate inflammation mainly through the IL-6, IL-1β, VEGFA, TNF-α, and PTGS2 (COX-2), and the NF-κB signaling pathways. This finding will provide clin. guidance for further research on the use of Kushen to treat inflammation.

Scientific Reports published new progress about Anti-inflammatory agents. 6882-68-4 belongs to class naphthyridine, and the molecular formula is C15H24N2O, Quality Control of 6882-68-4.

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