Category: naphthyridine

Taguchi, Y.-H. published the artcile< Drug candidate identification based on gene expression of treated cells using tensor decomposition-based unsupervised feature extraction for large-scale data>, HPLC of Formula: 1223001-51-1, the main research area is gene expression tensor decomposition extraction; Feature extraction; Gene expression; Tensor decomposition.

Although in silico drug discovery is necessary for drug development, two major strategies, a structure-based and ligand-based approach, have not been completely successful. Currently, the third approach, inference of drug candidates from gene expression profiles obtained from the cells treated with the compounds under study requires the use of a training dataset. Here, the purpose was to develop a new approach that does not require any pre-existing knowledge about the drug-protein interactions, but these interactions can be inferred by means of an integrated approach using gene expression profiles obtained from the cells treated with the analyzed compounds and the existing data describing gene-gene interactions. In the present study, using tensor decomposition-based unsupervised feature extraction, which represents an extension of the recently proposed principal-component anal.-based feature extraction, gene sets and compounds with a significant dose-dependent activity were screened without any training datasets. Next, after these results were combined with the data showing perturbations in single-gene expression profiles, genes targeted by the analyzed compounds were inferred. The set of target genes thus identified was shown to significantly overlap with known target genes of the compounds under study. The method is specifically designed for large-scale datasets (including hundreds of treatments with compounds), not for conventional small-scale datasets. The obtained results indicate that two compounds that have not been extensively studied, WZ-3105 and CGP-60474, represent promising drug candidates targeting multiple cancers, including melanoma, adenocarcinoma, liver carcinoma, and breast, colon, and prostate cancers, which were analyzed in this in silico study.

BMC Bioinformatics published new progress about Adenocarcinoma. 1223001-51-1 belongs to class naphthyridine, and the molecular formula is C24H15F3N4O, HPLC of Formula: 1223001-51-1.

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

Dai, Linlin; Wang, Luyao; Tan, Cheng; Cai, Jun; Shen, Hongsheng; Zhang, Ting; Zhi, Shuang; Yang, Zibo; Hu, Yunhui; Zhao, Xiumei; Li, Dongdong published the artcile< Sophoridine Derivatives Induce Apoptosis and Autophagy to Suppress the Growth of Triple-Negative Breast Cancer through Inhibition of mTOR Signaling>, 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 derivative preparation breast cancer apoptosis autophagy; autophagy; mTOR; sophoridine; triple-negative breast cancer.

In order to improve the antitumor potency and therapeutic margins of natural product sophoridine, its novel nitrogen mustard carbamate derivatives were designed and synthesized. In screening their in vitro activity, we found all the tested compounds were more potent against the highly aggressive triple-neg. breast cancer cell line MDA-MB-231. Cellular functional assays showed that representative compounds could induce G1-phase arrest and trigger apoptosis, evidenced by the alteration of Bax, Bcl-2, caspase-3 and PARP levels. Furthermore, these compounds significantly enhanced the autophagic flux with increased expression of LC3-II and Beclin-1, as well as decreased level of p62, which may attribute to simultaneously inhibition of the phosphorylation of p70S6K, 4E-BP1 and AKT, the key substrates of the mTOR signaling pathway. In vivo, two compounds revealed potent antitumor activity in mice bearing MDA-MB-231. Altogether, our work describes novel leads to yield more potent chemotherapeutics against triple-neg. breast cancers, possibly mesenchymal stem-like subtype.

ChemMedChem published new progress about Antiproliferative agents. 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

Ponsford, Amy H.; Ryan, Thomas A.; Raimondi, Andrea; Cocucci, Emanuele; Wycislo, Susanne A.; Frohlich, Florian; Swan, Laura E.; Stagi, Massimiliano published the artcile< Live imaging of intra-lysosome pH in cell lines and primary neuronal culture using a novel genetically encoded biosensor>, Safety of 9-(6-Aminopyridin-3-yl)-1-(3-(trifluoromethyl)phenyl)benzo[h][1,6]naphthyridin-2(1H)-one, the main research area is chloroquine fluorescence microscopy lysosome MTOR protein pH Vtype ATPase; Chloroquine; MTOR protein; V-type ATPase; fluorescence microscopy; lysosomes; pH.

Disorders of lysosomal physiol. have increasingly been found to underlie the pathol. of a rapidly growing cast of neurodevelopmental disorders and sporadic diseases of aging. One cardinal aspect of lysosomal (dys)function is lysosomal acidification in which defects trigger lysosomal stress signaling and defects in proteolytic capacity. We have developed a genetically encoded ratiometric probe to measure lysosomal pH coupled with a purification tag to efficiently purify lysosomes for both proteomic and in vitro evaluation of their function. Using our probe, we showed that lysosomal pH is remarkably stable over a period of days in a variety of cell types. Addnl., this probe can be used to determine that lysosomal stress signaling via TFEB is uncoupled from gross changes in lysosomal pH. Finally, we demonstrated that while overexpression of ARL8B GTPase causes striking alkalinization of peripheral lysosomes in HEK293 T cells, peripheral lysosomes per se are no less acidic than juxtanuclear lysosomes in our cell lines.

Autophagy published new progress about Acidification. 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

Lin, Beibei; Xu, Dingqiao; Wu, Sanqiao; Qi, Shanshan; Xu, Youmei; Liu, Xiang; Zhang, Xiaoying; Chen, Chen published the artcile< Antioxidant effects of Sophora davidi (Franch.) Skeels on D-galactose-induced aging model in mice via activating the SIRT1/p53 pathway>, COA of Formula: C15H24N2O, the main research area is Sophora aging SIRT1 p53 antioxidant; D-galactose; SIRT1; Sophora davidi (franch.) skeels fruits extract; anti-aging; p53.

This study investigated the protective effect of Sophora davidi (Franch.) Skeels fruits extract (SDE) on D-galactose-induced acute aging in mice. Ultra performance liquid chromatog. coupled with tine-of-flight mass spectrometry (UPLC-Q-TOF/MS) was performed to identify the composition of compounds in SDE. KM mice were divided stochastically into the normal control group (NC, saline), D-galactose (D-gal) model group, vitamin C (Vc) group (pos. control), low-, medium-and high-dose SDE treat groups. After 28 days administration and fasting overnight, the serum, liver, and brain samples of mice were collected. The levels of inducible nitric oxide synthase (iNOS), acetylcholinesterase (AChE) activity in the brain, malondialdehyde (MDA) and reduced glutathione (GSH) content, superoxide dismutase (SOD) and total antioxidant capacity (T-AOC) activity in the liver and brain were measured. Immunohistochem. was applied to detect silent information regulator 1 (SIRT1) and p53 protein expression in the liver and brain, and quant. real-time polymerase chain reaction (qRT-PCR) was used to detect the expression of nuclear factor κB (NF-κB), tumor necrosis factor (TNF-α), interleukin-6 (IL-6), interleukin-1β (IL-1β), and anti-aging factor Klotho in the liver and brain. The results showed that UPLC-Q-TOF/MS identified 78 compounds in SDE. SDE could reduce the iNOS activity in serum and AChE activity in the brain, upregulate the levels of SOD, T-AOC and GSH in liver and brain, and debase the MDA content in liver and brain. SDE could downregulate the mRNA expressions of TNF-α, NF-κB, IL-1β, and IL-6 in the liver and brain, and elevate the mRNA expression of Klotho. SDE improved the pathol. changes of the liver and brain induced by D-gal, increased the expression of SIRT1 protein in the liver and brain, and inhibited the expression of p53 protein induced by D-gal. To summarize, SDE demonstrated clear anti-aging effect, and its mechanism may be relevant to the activation of the SIRT1/p53 signal pathway.

Frontiers in Pharmacology published new progress about Aging, animal. 6882-68-4 belongs to class naphthyridine, and the molecular formula is C15H24N2O, COA of Formula: C15H24N2O.

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

Phan, Trong-Nhat; Baek, Kyung-Hwa; Lee, Nakyung; Byun, Soo Young; Shum, David; No, Joo Hwan published the artcile< In vitro and in vivo activity of mTOR kinase and PI3K inhibitors against Leishmania donovani and Trypanosoma brucei>, Application of C24H15F3N4O, the main research area is Leishmania Trypanosoma acute monocytic leukemia dactolisib Torin2 PI3K mTOR; Leishmania; Trypanosoma; inhibitors; mammalian target of rapamycin; phosphoinositide 3-kinase.

Kinetoplastid parasites, including Leishmania and Trypanosoma spp., are life threatening pathogens with a worldwide distribution. Next-generation therapeutics for treatment are needed as current treatments have limitations, such as toxicity and drug resistance. In this study, we examined the activities of established mammalian target of rapamycin (mTOR)/phosphoinositide 3-kinase (PI3K) inhibitors against these tropical diseases. High-throughput screening of a library of 1742 bioactive compounds against intracellular L. donovani was performed, and seven mTOR/PI3K inhibitors were identified. Dose-dilution assays revealed that these inhibitors had half maximal effective concentration (EC50) values ranging from 0.14 to 13.44 muM for L. donovani amastigotes and from 0.00005 to 8.16 muM for T. brucei. The results of a visceral leishmaniasis mouse model indicated that treatment with Torin2, dactolisib, or NVP-BGT226 resulted in reductions of 35%, 53%, and 54%, resp., in the numbers of liver parasites. In an acute T. brucei mouse model using NVP-BGT226 parasite numbers were reduced to under the limits of detection by five consecutive days of treatment. Multiple sequence and structural alignment results indicated high similarities between mTOR and kinetoplastid TORs; the inhibitors are predicted to bind in a similar manner. Taken together, these results indicated that the TOR pathways of parasites have potential for the discovery of novel targets and new potent inhibitors.

Molecules published new progress about Acute monocytic leukemia. 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

Wang, Han; Xu, Xiuli; Wang, Xiujuan; Guo, Wei; Jia, Wei; Zhang, Feng published the artcile< An analytical strategy for discovering structural analogues of alkaloids in plant food using characteristic structural fragments extraction by high resolution orbitrap mass spectrometry>, Recommanded Product: (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 alkaloid plant food fragment extraction mass spectrometry.

Structural analogs of alkaloids are a huge risk for food safety. However, the discovery of potentially homolog-type alkaloids remains a challenge. A new strategy for discovering structural analogs of alkaloids using high resolution mass spectrometry under data independent acquisition was established using extracted characteristic ions chromatograms and mass spectrometry fragmentations pathway, and successfully developed for discovering and identificating multiple classes of alkaloids in plant food. In this work, we selected 24 alkaloids (pyrrolizidine alkaloids, solanine-type alkaloids, matrine-type alkaloids) as target compounds The data acquisition was based on a non-target approach of data independent acquisition. The general workflow of structural analogs of alkaloids confirming strategy can be split into four major stages: (i) the pathway of fragmentation clarifying, (ii) characteristic structural fragments filtering and confirming, (iii) structural analogs of alkaloids discovery method establishing, (iv) real sample anal. This scheme provided an efficient confirming method for discovering structural analogs of alkaloids in plant food.

LWT–Food Science and Technology 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, Recommanded Product: (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

Liu, Zhichao; Chen, Xi; Roberts, Ruth; Huang, Ruili; Mikailov, Mike; Tong, Weida published the artcile< Unraveling gene fusions for drug repositioning in high-risk neuroblastoma>, Safety of 9-(6-Aminopyridin-3-yl)-1-(3-(trifluoromethyl)phenyl)benzo[h][1,6]naphthyridin-2(1H)-one, the main research area is neuroblastoma gene fusion drug repositioning; drug repositioning; gene fusions; neuroblastoma; next-generation sequencing; precision medicine 3; structural variants.

High-risk neuroblastoma (NB) remains a significant therapeutic challenge facing current pediatric oncol. patients. Structural variants such as gene fusions have shown an initial promise in enhancing mechanistic understanding of NB and improving survival rates. In this study, we performed a comprehensive in silico investigation on the translational ability of gene fusions for patient stratification and treatment development for high-risk NB patients. Specifically, three state-of-the-art gene fusion detection algorithms, including ChimeraScan, SOAPfuse, and TopHat-Fusion, were employed to identify the fusion transcripts in a RNA-seq data set of 498 neuroblastoma patients. Then, the 176 high-risk patients were further stratified into four different subgroups based on gene fusion profiles. Furthermore, Kaplan-Meier survival anal. was performed, and differentially expressed genes (DEGs) for the redefined high-risk group were extracted and functionally analyzed. Finally, repositioning candidates were enriched in each patient subgroup with drug transcriptomic profiles from the LINCS L1000 Connectivity Map. We found the number of identified gene fusions was increased from clin. the low-risk stage to the high-risk stage. Although the tech. concordance of fusion detection algorithms was suboptimal, they have a similar biol. relevance concerning perturbed pathways and regulated DEGs. The gene fusion profiles could be utilized to redefine high-risk patient subgroups with significant onset age of NB, which yielded the improved survival curves (Log-rank p value le 0.05). Out of 48 enriched repositioning candidates, 45 (93.8%) have antitumor potency, and 24 (50%) were confirmed with either on-going clin. trials or literature reports. The gene fusion profiles have a discrimination power for redefining patient subgroups in high-risk NB and facilitate precision medicine-based drug repositioning implementation.

Frontiers in Pharmacology 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

Zhao, Yi-Shu; Qian, Xing-Kai; Guan, Xiao-Qing; Song, Pei-Fang; Song, Yun-Qing; He, Rong-Jing; Sun, Meng-Ru; Wang, Xiu-Yang; Zou, Li-Wei; Ge, Guang-Bo published the artcile< Discovery of natural alkaloids as potent and selective inhibitors against human carboxylesterase 2>, 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 natural alkaloid screening carboxylesterase inhibitor structure; Alkaloids; Human carboxylesterase 2A (hCES2A); Inhibitor; Reserpine.

Human Carboxylesterase 2A (hCES2A), one of the most important serine hydrolases, plays crucial roles in the hydrolysis and the metabolic activation of a wide range of esters and amides. Increasing evidence has indicated that potent inhibition on intestinal hCES2A may reduce the excessive accumulation of SN-38 (the hydrolytic metabolite of irinotecan with potent cytotoxicity) in the intestinal tract and thereby alleviate the intestinal toxicity triggered by irinotecan. In this study, more than sixty natural alkaloids have been collected and their inhibitory effects against hCES2A are assayed using a fluorescence-based biochem. assay. Following preliminary screening, seventeen alkaloids are found with strong to moderate hCES2A inhibition activity. Primary structure-activity relationships (SAR) anal. of natural isoquinoline alkaloids reveal that the benzo-1,3-dioxole group and the aromatic pyridine structure are beneficial for hCES2A inhibition. Further investigations demonstrate that a steroidal alkaloid reserpine exhibits strong hCES2A inhibition activity (IC50 = 0.94μM) and high selectivity over other human serine hydrolases including hCES1A, dipeptidyl peptidase IV (DPP-IV), butyrylcholinesterase (BChE) and thrombin. Inhibition kinetic analyses demonstrated that reserpine acts as a non-competitive inhibitor against hCES2A-mediated FD hydrolysis. Mol. docking simulations demonstrated that the potent inhibition of hCES2A by reserpine could partially be attributed to its strong σ-π and S-π interactions between reserpine and hCES2A. Collectively, our findings suggest that reserpine is a potent and highly selective inhibitor of hCES2A, which can be served as a promising lead compound for the development of more efficacious and selective alkaloids-type hCES2A inhibitors for biomedical applications.

Bioorganic Chemistry published new progress about Alkaloids Role: PAC (Pharmacological Activity), THU (Therapeutic Use), BIOL (Biological Study), USES (Uses). 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

Huo, Zhixia; Chen, Lei published the artcile< Base-deactivated and alkaline-resistant chromatographic stationary phase based on functionalized polymethylsilsesquioxane microspheres>, Formula: C15H24N2O, the main research area is base deactivated chromatog stationary phase functionalized polymethylsilsesquioxane microsphere; basic compounds; co-condensation; functionalization; polymethylsilsesquioxane; silanol activity.

Vinyl, chloropropyl, and mercaptopropyl functionalized particles were prepared by a two-step acidic/alk. catalyzed co-hydrolysis/condensation of methyltrimethoxysilane with a different silane precursor that carries chem. reactive functional group including vinyl, chloropropyl, and mercaptopropyl, resp. The morphol., pore structure, and functional groups of the synthesized packings were studied by SEM, nitrogen adsorption-desorption measurements, and solid-state 13C 29Si NMR spectroscopy, resp. The particles show ordered sphere, narrow particle size distribution, and mesoporous structure. The carbon contents of the microspheres are in the range of 17-19%, comparable to those of octadecyl-bonded silica packings. The three-kind of microspheres were directly used as packing materials for high-performance liquid chromatog. without size classification. The chromatog. performance of the columns was evaluated and compared with a com. available C18 phase. The results revealed that these columns possess typical reversed-phase chromatog. properties with increased hydrophobicity than polymethylsilsesquioxane and sym. peaks for basic compounds They were applied to the simultaneous separation of combination bendazol hydrochlorothiazide capsules containing polar and basic drugs with peaks identified by tandem with mass spectrometry. In general, a novel method is provided for the synthesis of different methyltrimethoxysilane-derived microspheres for high-performance liquid chromatog., which are advantageous for separating basic compounds

Journal of Separation Science published new progress about Chromatographic stationary phases (base-deactivated and alk.-resistant). 6882-68-4 belongs to class naphthyridine, and the molecular formula is C15H24N2O, Formula: C15H24N2O.

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

Zhang, Zhengyi; Xie, Ziye; Lv, Shujing; Shi, Yulian; Zhai, Chuanjia; Li, Xuejiao; Qiao, Bin; Gao, Xiaoyan published the artcile< Integrated metabolomics and network pharmacology study on the mechanism of Kangfuxiaoyan suppository for treating chronic pelvic inflammatory disease>, 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 pelvic inflammatory disease Kangfuxiaoyan suppository metabolomic UPLCQTOFMS pharmacokinetic antiinflammatory; UPLC-Q-TOF/MS; chronic pelvic inflammatory disease; kangfuxiaoyan suppository; metabolomics; network pharmacology.

Kangfuxiaoyan suppository (KFXYS) is a commonly used traditional Chinese medicine (TCM) preparation for the treatment of chronic pelvic inflammatory disease (CPID) clin., and its safety and effectiveness have been well verified. However, the potential mechanism remains unclear. The integrated strategy of metabolomics and network pharmacol. was employed in the study to reveal the potential mechanism of KFXYS in the treatment of CPID. Our research consists of five steps. First, the effect of KFXYS in reversing uterine inflammation indexes was verified. Second, based on the comprehensive characterization of 123 chem. ingredients of KFXYS, the ingredients of KFXYS absorbed into blood were identified by UPLC-Q-TOF/MS, then ADME research was carried out on the main ingredients. Third, the differential metabolites with significant correlation to inflammatory indexes were discovered by metabolomics and correlation anal. Fourth, the potential targets and pathways of KFXYS in treating CPID were predicted by network pharmacol. based on the ingredients which had good ADME behavior. Fifth, the proteins in common pathways of metabolomics and network pharmacol. were used to screen the key targets from the potential targets of network pharmacol., and the potential mechanism of KFXYS in treating CPID was clarified. As a result, KFXYS significantly reversed the uterine inflammation indexes, including IL-1 and IL-6. The ingredients absorbed into blood including matrine, sophocarpine, aloin, esculetin-O-glucuronide, 7,4″”-dihydroxyisoflavone-O-glucuronide, and 4″”-methoxyisoflavone-7-O-glucuronide had good ADME behavior in vivo. Among the differential metabolites, Leukotriene A4, 5- Hydroxyindoleacetic acid, Ornithine, Arginine, and PC (20:1 (11Z)/20:4 (8Z,11Z,14Z,17Z)) were significant correlation to inflammation indexes. The integration anal. of metabolomics and network pharmacol. shows that KFXYS may regulate the key targets including ARG1, NOS2, NOS3, etc. We speculate that ingredients of KFXYS, such as matrine, sophocarpine, aloin etc. act on the key proteins including ARG1, NOS2, and NOS3, to exert anti-inflammatory effect.

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, 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