Heterocyclic Building Blocks-Naphthyridine

Zhang, Lei; Yang, Xingxing; Liu, Juanjuan; Luo, Yan; Li, Zhiyuan; Ji, Xinmiao; Wang, Wenchao; Zhang, Xin published the artcile< 1 T moderate intensity static magnetic field affects Akt/mTOR pathway and increases the antitumor efficacy of mTOR inhibitors in CNE-2Z cells>, COA of Formula: C24H15F3N4O, the main research area is Torin2 magnetic field anticancer agent Akt mTOR nasopharyngeal carcinoma.

Static magnetic field (SMF) has been known to affect cell proliferation in a cell-type-dependent manner, while the mechanism still remains unclear. We found that 1 T moderate intensity SMF inhibits cell proliferation of nasopharyngeal carcinoma CNE-2Z cells and the Akt/mTOR signaling pathway, which is upregulated in many cancers. mTOR inhibitors are potential chemodrugs, but their clin. effects are limited by the feedback reactivation of other signaling components such as EGFR and Akt. We showed that 1 T SMF increases the antitumor efficacy of mTOR inhibitor Torin 2. In addition, 1 T SMF increases the inhibition efficiency on mTOR substrates phosphorylation and represses the mTOR inhibitor-induced feedback reactivation of EGFR and Akt. Our study not only demonstrates that mTOR/Akt pathway is one of the mol. targets of SMFs in cells, but also reveals the clin. potentials of combinations of mTOR inhibitors and SMFs in cancer treatment.

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

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

Yu, Bo; Diao, Nan-Nan; Zhang, Ying; Li, Xing-Zi; Yu, Ning; Ding, Yang-Feng; Shi, Yu-Ling published the artcile< Network pharmacology-based identification for therapeutic mechanisms of Dangguikushen pill in acne vulgaris>, 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 Dangguikushen pill acne vulgaris network pharmacol therapeutic mechanism; Dangguikushen pill; acne vulgaris; mechanisms; network pharmacology; pathway; therapeutic target; traditional Chinese medicine.

The Dangguikushen (DGKS) pill is a proprietary traditional Chinese medicine that has shown superior efficacy in the treatment of acne vulgaris for many years. A network pharmacol.-based anal. was performed to explore the potential anti-acne compounds, core therapeutic targets, and the main pathways, involved in the DGKS pill bioactivity. The matching results between the predicted targets of the DGKS pill and the well-known targets of acne vulgaris were collected, followed by network establishment using protein-protein interaction (PPI) data. Cytoscape was utilized to analyze the network and screen the core targets. Furthermore, the Database for Annotation, Visualization and Integrated Discovery (DAVID), and ClueGO were used for the enrichment anal. of the Kyoto Encyclopedia of Genes and Genomics (KEGG) pathways and Gene Ontol. biol. processes (GO-BP). Finally, the “”compound-target-pathway”” network was constructed. This approach identified 19 active compounds, 46 therapeutic targets, and 12 core therapeutic targets of the DGKS pill. The biol. processes were primarily related to reactive oxygen species (ROS) metabolic process, gland morphogenesis, and female gonad development. The DGKS pill was significantly associated with eight pathways including the PI3K-Akt, TNF, NF-kappa B, and p53 signaling pathways. DGKS pill might have a synergistic effect on the inhibition of excessive sebaceous lipogenesis and sebocyte differentiation, and likewise, anti-inflammatory effects via the different signaling pathways (PI3K-Akt, TNF, NF-kappa B, and p53).

Dermatologic Therapy published new progress about Acne vulgaris. 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

Feehan, Robert P.; Shantz, Lisa M. published the artcile< Negative regulation of the FOXO3a transcription factor by mTORC2 induces a pro-survival response following exposure to ultraviolet-B irradiation>, Application of C24H15F3N4O, the main research area is UVB radiation FOXO3a mTORC2 cell survival skin cancer; Apoptosis; Cancer chemoprevention; FOXO; Keratinocyte; Mammalian target of rapamycin (mTOR); UVB.

Exposure to UV-B (UVB) irradiation, the principal cause of non-melanoma skin cancer (NMSC), activates both the rapamycin-sensitive mammalian target of rapamycin complex 1 (mTORC1) and the rapamycin-resistant mTORC2. We have previously reported that UVB-induced keratinocyte survival is dependent on mTORC2, though the specific mechanism is not well understood. FOXO3a is an important transcription factor involved in regulating cell survival. The activity of FOXO3a is reduced as a result of protein kinase B (AKT/PKB) activation, which is downstream of mTORC2; however, the specific function of FOXO3a during UVB-induced apoptosis is unclear. In this study, we establish that in cells with wild-type mTORC2 activity, FOXO3a is quickly phosphorylated in response to UVB and sequestered in the cytoplasm. In contrast, loss of mTORC2 causes FOXO3a to be localized to the nucleus and sensitizes cells to UVB-induced apoptosis. Furthermore, this sensitization is rescued by knockdown of FOXO3a. Taken together, these studies provide strong evidence that inhibition of mTORC2 enhances UVB-induced apoptosis in a FOXO3a-dependent manner, and suggest that FOXO3a activation by mTORC2 inhibitors may be a valuable chemopreventive target in NMSC.

Cellular Signalling published new progress about Apoptosis. 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

Malik, Nasir; Manickam, Rohini; Bachani, Muznabanu; Steiner, Joseph P. published the artcile< A strategy to identify compounds that affect cell growth and survival in cultured mammalian cells at low-to-moderate throughput>, Name: 9-(6-Aminopyridin-3-yl)-1-(3-(trifluoromethyl)phenyl)benzo[h][1,6]naphthyridin-2(1H)-one, the main research area is growth cultured mammalian neural stem cell.

Cytotoxicity is a critical parameter that needs to be quantified when studying drugs that may have therapeutic benefits. Because of this, many drug screening assays utilize cytotoxicity as one of the critical characteristics to be profiled for individual compounds Cells in culture are a useful model to assess cytotoxicity before proceeding to follow up on promising lead compounds in more costly and labor-intensive animal models. We describe a strategy to identify compounds that affect cell growth in a tdTomato expressing human neural stem cells (NSC) line. The strategy uses two complementary assays to assess cell number One assay works via the reduction of 3-(4,5-dimethylthizol-2-yl)-2,5- diphenyltetrazolium bromide (MTT) to formazan as a proxy for cell number and the other directly counts the tdTomato expressing NSCs. The two assays can be performed simultaneously in a single experiment and are not labor intensive, rapid, and inexpensive. The strategy described in this demonstration tested 57 compounds in an exploratory primary screen for toxicity in a 96-well plate format. Three of the hits were characterized further in a six-point dose response using the same assay set-up as the primary screen. In addition to providing excellent corroboration for toxicity, comparison of results from the two assays may be effective in identifying compounds affecting other aspects of cell growth.

Journal of Visualized Experiments published new progress about Cell enlargement. 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

Ren, Gang; Ding, Guotao; Zhang, Hongyan; Wang, Haipeng; Jin, Zengjun; Yang, Guoxing; Han, Yonghong; Zhang, Xia; Li, Guiying; Li, Weihao published the artcile< Antiviral activity of sophoridine against enterovirus 71 in vitro>, Reference of 6882-68-4, the main research area is sophoridine enterovirus antiviral activity; Antiviral activity; Cytopathic effect; Enterovirus 71; Sophoridine; Viral adsorption.

Enterovirus 71 (EV71) has a propensity to cause hand-foot-and-mouth disease (HFMD) epidemics associated with neurol. sequelae. Unfortunately, no drugs are currently available for the clin. treatment of EV71 infections. Sophoridine (SRI) is one of the most abundant alkaloids in Sophora flavescens Aiton (Leguminosae), which has been used to treat fever, throat inflammation, cancer, and other diseases. In this study, we found that SRI inhibits EV71 infection in Vero cells. To study the antiviral activity of SRI, Vero cells were divided into 3 treatment groups based on the timing of SRI dosing: prior to viral adsorption (Group A), during viral adsorption (Group B), and after viral adsorption (Group C). We further revealed the antiviral activity of SRI with the attachment assay and the penetration assay. For Group A, 50% viability of Vero cells was observed at a SRI concentration of 61.39μg/mL, whereas for Groups B, 50% viability was observed at SRI concentrations of 196.86μg/mL. Furthermore, 29.7% cell viability was observed even at a SRI concentration of 1000μg/mL in Groups C. The results show that SRI was highly effective against EV71 when Vero cells were pretreated with SRI for 2 h (Group A). Further researches indicate SRI was highly effective at inhibiting EV71 attachment when the SRI concentrations over 250μg/mL (P < 0.001). We have shown that Vero cell viability increases when SRI is administered prior to viral adsorption. This suggests that SRI has the considerable potential as an antiviral for EV71 disease prevention. Journal of Ethnopharmacology published new progress about Antiviral agents. 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

Tavares, Catarina; Eloy, Catarina; Melo, Miguel; da Rocha, Adriana Gaspar; Pestana, Ana; Batista, Rui; Ferreira, Luciana Bueno; Rios, Elisabete; Simoes, Manuel Sobrinho; Soares, Paula published the artcile< mTOR pathway in papillary thyroid carcinoma: different contributions of mTORC1 and mTORC2 complexes for tumor behavior and SLC5A5 mRNA expression>, Electric Literature of 1223001-51-1, the main research area is PTC mTORC tumor behavior SLCA mTOR pathway; mTOR; sodium iodide symporter (NIS)/SLC5A5; thyroid cancer.

The mammalian target of rapamycin (mTOR) pathway is overactivated in thyroid cancer (TC). We previously demonstrated that phospho-mTOR expression is associated with tumor aggressiveness, therapy resistance, and lower mRNA expression of SLC5A5 in papillary thyroid carcinoma (PTC), while phospho-S6 (mTORC1 effector) expression was associated with less aggressive clinicopathol. features. The distinct behavior of the two markers led us to hypothesize that mTOR activation may be contributing to a preferential activation of the mTORC2 complex. To approach this question, we performed immunohistochem. for phospho-AKT Ser473 (mTORC2 effector) in a series of 182 PTCs previously characterized for phospho-mTOR and phospho-S6 expression. We evaluated the impact of each mTOR complex on SLC5A5 mRNA expression by treating cell lines with RAD001 (mTORC1 blocker) and Torin2 (mTORC1 and mTORC2 blocker). Phospho-AKT Ser473 expression was pos. correlated with phospho-mTOR expression. Nuclear expression of phospho-AKT Ser473 was significantly associated with the presence of distant metastases. Treatment of cell lines with RAD001 did not increase SLC5A5 mRNA levels, whereas Torin2 caused a ∼6 fold increase in SLC5A5 mRNA expression in the TPC1 cell line. In PTC, phospho-mTOR activation may lead to the activation of the mTORC2 complex. Its downstream effector, phospho-AKT Ser473, may be implicated in distant metastization, therapy resistance, and downregulation of SLC5A5 mRNA expression.

International Journal of Molecular Sciences published new progress about Animal gene Role: BSU (Biological Study, Unclassified), PRP (Properties), BIOL (Biological Study) (BRAF). 1223001-51-1 belongs to class naphthyridine, and the molecular formula is C24H15F3N4O, Electric Literature of 1223001-51-1.

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

Garcia, Gustavo; Sharma, Arun; Ramaiah, Arunachalam; Sen, Chandani; Purkayastha, Arunima; Kohn, Donald B.; Parcells, Mark S.; Beck, Sebastian; Kim, Heeyoung; Bakowski, Malina A.; Kirkpatrick, Melanie G.; Riva, Laura; Wolff, Karen C.; Han, Brandon; Yuen, Constance; Ulmert, David; Purbey, Prabhat K.; Scumpia, Phillip; Beutler, Nathan; Rogers, Thomas F.; Chatterjee, Arnab K.; Gabriel, Gulsah; Bartenschlager, Ralf; Gomperts, Brigitte; Svendsen, Clive N.; Betz, Ulrich A. K.; Damoiseaux, Robert D.; Arumugaswami, Vaithilingaraja published the artcile< Antiviral drug screen identifies DNA-damage response inhibitor as potent blocker of SARS-CoV-2 replication>, COA of Formula: C24H15F3N4O, the main research area is human covid antiviral drug screening DNA damage response inhibitor; ATR kinase; COVID-19; DNA-damage response pathway; SARS-CoV-2; berzosertib; high-throughput screen; mTOR-PI3K-AKT pathway; nucleoside analogs; protein kinase inhibitors.

SARS-CoV-2 has currently precipitated the COVID-19 global health crisis. We developed a medium-throughput drug-screening system and identified a small-mol. library of 34 of 430 protein kinase inhibitors that were capable of inhibiting the SARS-CoV-2 cytopathic effect in human epithelial cells. These drug inhibitors are in various stages of clin. trials. We detected key proteins involved in cellular signaling pathways mTOR-PI3K-AKT, ABL-BCR/MAPK, and DNA-damage response that are critical for SARS-CoV-2 infection. A drug-protein interaction-based secondary screen confirmed compounds, such as the ATR kinase inhibitor berzosertib and torin2 with anti-SARS-CoV-2 activity. Berzosertib exhibited potent antiviral activity against SARS-CoV-2 in multiple cell types and blocked replication at the post-entry step. Berzosertib inhibited replication of SARS-CoV-1 and the Middle East respiratory syndrome coronavirus (MERS-CoV) as well. Our study highlights key promising kinase inhibitors to constrain coronavirus replication as a host-directed therapy in the treatment of COVID-19 and beyond as well as provides an important mechanism of host-pathogen interactions.

Cell Reports published new progress about Antiviral agents. 1223001-51-1 belongs to class naphthyridine, and the molecular formula is C24H15F3N4O, COA of Formula: C24H15F3N4O.

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

Chen, Mengchun; Jiang, Qi; Zhang, Mingyao; Chen, Sailing; Lou, Junsheng; Chen, Yijie; Wang, Fang; Wang, Rongyue published the artcile< Establishment of quantitative methodology for sophoridine analysis and determination of its pharmacokinetics and bioavailability in rat>, Reference of 6882-68-4, the main research area is sophoridine detection blood circulation pharmacokinetics bioavailability rat; Sophoridine; UPLC–MS/MS; bioavailability; pharmacokinetics; rat plasma.

The aim of this study is to develop a rapid and sensitive UPLC-MS/MS approach to determine the sophoridine (SOP) level in rat plasma and the pharmacokinetics of the substance. Sophoridine is used as an anti-inflammatory, anti-virus, anti-microbial, and anti-tumor alkaloid. It is essential to explore specific detection methods for the quant. anal. of SOP in the blood circulation. The rat plasma samples were prepared by one-step protein precipitation with acetonitrile. Subsequently, the samples were separated by chromatog. using a UPLC BEH C18 reversed-phase with an initial mobile phase of methanol and 0.1% formic acid aqueous solution The gradient elution was performed at a fixed flow rate of 0.4 mL/min, and multiple reaction monitoring (MRM) mode with an electrospray pos. ionization source was employed to detect the transitions of m/z 249.1 → 84.2 for SOP and m/z 264.3 → 69.8 for dendrobine (IS). The entire process required 3.5 min for each sample. A linear correlation was established over the range of 2-2000 ng/mL (r2≥0.9954) for SOP in rat plasma with a lower limit of quantification (LLOQ) at 2 ng/mL. The range of accuracy was tested between 94.90% and 100.80%, and the relative standard deviations (RSDs) toward both intra- and inter-day precision were <10%. Thus, this method was successfully applied to a pharmacokinetic study, and the subsequent results demonstrated a low absolute bioavailability of 2.32%. The present study established a reliable method that quantified the SOP concentration in rat plasma after administering a dose of 2 mg/kg i.v. or 20 mg/kg orally. Drug Development and Industrial Pharmacy published new progress about Alkaloids Role: ANT (Analyte), BSU (Biological Study, Unclassified), THU (Therapeutic Use), ANST (Analytical Study), BIOL (Biological Study), USES (Uses). 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

Li, Jian-Chun; Zhang, Zhi-Jun; Liu, Dan; Jiang, Ming-Yan; Li, Rong-Tao; Li, Hong-Mei published the artcile< Quinolizidine alkaloids from the roots of Sophora flavescens>, Electric Literature of 6882-68-4, the main research area is quinolizidine alkaloid isolation Sophora flavescens cancer inflammation; Sophora; Sophora flavescens Alt; anti-inflammation; cytotoxicity; quinolizidine alkaloids.

Seventeen quinolizidine alkaloids, including a new matrine-type one, sophcence A, were isolated from the roots of Sophora flavescens Alt. The structure of compound was elucidated by means of 1D and 2D NMR, as well as HR-ESI-MS spectroscopic data. The NMR data of (-)-Δ7-dehydrosophoramine () and oxy-N-methylcytisine () were reported for the first time. In addition, (+)-sophoranol () exhibited moderate inhibition on lipopolysaccharide (LPS)-induced nitric oxide (NO) production in RAW 264.7 macrophages with IC50 value of 22.14 μM, while lupanine () was found to inhibit the growth of human glioma stem cells GSC-3# at 20 μg/mL.

Natural Product Research published new progress about Alkaloids Role: NPO (Natural Product Occurrence), PAC (Pharmacological Activity), PUR (Purification or Recovery), THU (Therapeutic Use), BIOL (Biological Study), OCCU (Occurrence), PREP (Preparation), USES (Uses). 6882-68-4 belongs to class naphthyridine, and the molecular formula is C15H24N2O, Electric Literature of 6882-68-4.

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

Zhou, Wei; Wu, Jiarui; Zhang, Jingyuan; Liu, Xinkui; Guo, Siyu; Jia, ShanShan; Zhang, Xiaomeng; Zhu, Yingli; Wang, Miaomiao published the artcile< Integrated bioinformatics analysis to decipher molecular mechanism of compound Kushen injection for esophageal cancer by combining WGCNA with network pharmacology>, Reference of 6882-68-4, the main research area is esophageal cancer Kushen injection pharmacol bioinformatics.

Compound Kushen injection (CKI), a medicine in widespread clin. use in China, has proven therapeutic effects on cancer. However, few mol. mechanism analyses have been carried out. To address this problem, bioinformatics approaches combining weighted gene co-expression network anal. with network pharmacol. methods were undertaken to elucidate the underlying mol. mechanisms of CKI in the treatment of esophageal cancer (ESCA). First, the key gene modules related to the clin. traits of ESCA were analyzed by WCGNA. Based on the results, the hub genes related to CKI treatment for ESCA were explored through network pharmacol. Mol. docking simulation was performed to recognize the binding activity of hub genes with CKI compounds The results showed that the potential hub targets, including EGFR, ErbB2, CCND1 and IGF1R, are therapeutic targets of CKI for the treatment of ESCA. Moreover, these targets were significantly enriched in many pathways related to cancer and signalling pathways, such as the PI3K-Akt signalling pathway and ErbB signalling pathway. In conclusion, this research partially highlighted the mol. mechanism of CKI in the treatment of ESCA, offering great potential in the identification of the effective compounds in CKI and biomarkers for ESCA treatment.

Scientific Reports published new progress about Animal gene, c-erbB 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