Heterocyclic Building Blocks-Naphthyridine

Wei, Guangfei; Chen, Yongzhong; Guo, Xiaotong; Wei, Jianhe; Dong, Linlin; Chen, Shilin published the artcile< Biosyntheses characterization of alkaloids and flavonoids in Sophora flavescens by combining metabolome and transcriptome>, Application of C15H24N2O, the main research area is Sophora flavescens alkaloid flavonoid metabolome transcriptome biosynthesis.

Sophora flavescens are widely used for their pharmacol. effects. As its main pharmacol. components, alkaloids and flavonoids are distributed in the root tissues wherein mol. mechanisms remain elusive. In this study, metabolite profiles are analyzed using metabolomes to obtain biomarkers detected in different root tissues. These biomarkers include alkaloids, phenylpropanoids, and flavonoids. The high-performance liquid chromatog. anal. results indicate the differences in principal component contents. Oxymatrine, sophoridine, and matrine contents are the highest in the phloem, whereas trifolirhizin, maackiain, and kushenol I contents are the highest in the xylem. The transcript expression profiles also show tissue specificity in the roots. A total of 52 and 39 transcripts involved in alkaloid and flavonoid syntheses are found, resp. Among them, the expression levels of LYSA1, LYSA2, AO2, AO6, PMT1, PMT17, PMT34, and PMT35 transcripts are highly and pos. correlated with alkaloids contents. The expression levels of 4CL1, 4CL3, 4CL12, CHI5, CHI7, and CHI9 transcripts are markedly and pos. correlated with flavonoids contents. Moreover, the quant. profiles of alkaloids and flavonoids are provided, and the pivotal genes regulating their distribution in S. flavescens are determined These results contribute to the existing data for the genetic improvement and target breeding of S. flavescens.

Scientific Reports 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, Application of C15H24N2O.

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

Ishikawa, Makoto; Takaseki, Sanae; Yoshitomi, Takeshi; Covey, Douglas F.; Zorumski, Charles F.; Izumi, Yukitoshi published the artcile< The neurosteroid allopregnanolone protects retinal neurons by effects on autophagy and GABRs/GABAA receptors in rat glaucoma models>, Quality Control of 1223001-51-1, the main research area is neurosteroid allopregnanolone GABR GABA receptor rat glaucoma model; Allopregnanolone; autophagy; glaucoma; intraocular pressure; neurosteroid.

In an ex vivo rat glaucoma model using dissected retinas, the neurosteroid allopregnanolone (AlloP) protects retinal ganglion cells (RGCs) via GABR/GABAA receptors. To determine the involvement of macroautophagy/autophagy in neuroprotection by AlloP, we examined the effects of autophagy activators, rapamycin and torin 2, and autophagy inhibitors, bafilomycin A1 and SAR405, on retinal retinal morphol. and expression of MAP1 LC3B/LC3B (microtubule-associated protein 1 light chain 3 beta) and SQSTM1 (sequestosome 1). Administration of rapamycin or torin 2 exerted partial histol. neuroprotection, while combined administration of AlloP with bafilomycin A1 or SAR405 induced severe degeneration in a hyperbaric condition. Electron microscopic analyses showed that the addition of AlloP significantly increased autophagosomes and degenerative autophagic vacuoles in the retinal nerve fiber layer. Immunoblotting showed that the addition of AlloP or autophagic activators increased the lipidated form of LC3B (LC3B-II) and suppressed SQSTM1. Moreover, bafilomycin A1 increased LC3B-II and SQSTM1 protein levels in the presence of AlloP without changes in corresponding mRNAs compared to AlloP-treated retinas in a hyperbaric condition. These data indicate that AlloP likely induces a protective form of autophagy in this model. In an in vivo rat model of glaucoma, we also observed neuroprotective effects of AlloP. Injection of polystyrene microbeads into the anterior chamber increased intraocular pressure about 3-fold and induced RGC apoptosis. A single intravitreal injection of AlloP or autophagy activators prevented apoptosis and protected RGCs with autophagy activation. We conclude that AlloP may serve as a potential therapeutic agent for the treatment of glaucoma via diverse mechanisms.

Autophagy published new progress about Apoptosis. 1223001-51-1 belongs to class naphthyridine, and the molecular formula is C24H15F3N4O, Quality Control of 1223001-51-1.

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

Shen, Chen; Chen, Jin Hong; Lee, Youngyi; Hassan, Mehedi Md.; Kim, Su Jin; Choi, Eun Young; Hong, Seong-Tshool; Park, Byung-Hyun; Park, Ji Hyun published the artcile< mTOR- and SGK-mediated connexin 43 expression participates in lipopolysaccharide-stimulated macrophage>, Product Details of C24H15F3N4O, the main research area is mTOR SGK connexin43 peritoneal macrophage bacterial peritonitis.

Connexin 43 (Cx43) deficiency was found to increase mortality in a mouse model of bacterial peritonitis, and Cx43 is upregulated in macrophages by LPS treatment. In this study, we characterized a novel signaling pathway for LPS-induced Cx43 expression in RAW264.7 cells and thioglycolate-elicited peritoneal macrophages (TGEMs). LPS alone or LPS-containing conditioned medium (CM) upregulated Cx43. Overexpression or silencing of Cx43 led to the enhancement or inhibition, resp., of CM-induced TGEM migration. This response involved the inducible NO synthase (iNOS)/focal adhesion kinase (FAK)/Src pathways. Moreover, CM-induced migration was compromised in TGEMs from Cx43+/2 mice compared with TGEMs from Cx43+/+ littermates. Cx43 was upregulated by a serum/glucocorticoid-regulated kinase 1 (SGK) activator and downregulated, along with inhibition of CM-induced TGEM migration, by knockdown of the SGK gene or blockade of the SGK pathway. LPS-induced SGK activation was abrogated by Torin2, whereas LPS-induced Cx43 was downregulated by both Torin2 and rapamycin. Anal. of the effects of FK506 and methylprednisolone, common immunosuppressive agents following organ transplantation, suggested a link between these immunosuppressive drugs and impaired macrophage migration via the Cx43/iNOS/Src/FAK pathway. In a model of Escherichia coli infectious peritonitis, GSK650349-, an SGK inhibitor, or Torin2-treated mice showed less accumulation of F4/80+CD11b+ macrophages in the peritoneal cavity, with a delay in the elimination of bacteria. Furthermore, following pretreatment with Gap19, a selective Cx43 hemichannel blocker, the survival of model mice was significantly reduced. Taken together, our study suggested that Cx43 in macrophages was associated with macrophage migration, an important immune process in host defense to infection.

Journal of Immunology published new progress about Adhesion G protein-coupled receptor E1 Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 1223001-51-1 belongs to class naphthyridine, and the molecular formula is C24H15F3N4O, Product Details of C24H15F3N4O.

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

Lei, Lijing; Zhao, Yu; Shi, Kai; Liu, Ying; Hu, Yunxia; Shao, Hua published the artcile< Phytotoxic activity of alkaloids in desert plant Sophora alopecuroides>, Safety of (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 phytotoxic activity oxymatrine Sophora desert plant; Sophora alopecuroides L.; abscisic acid (ABA); alkaloids; allelopathy; antioxidant defense system; cytokinin (CTK); indole-3-acetic acid (IAA); malondialdehyde (MDA).

Sophora alopecuroides is known to produce relatively large amounts of alkaloids; however, their ecol. consequences remain unclear. In this study, we evaluated the allelopathic potential of the main alkaloids, including aloperine, matrine, oxymatrine, oxysophocarpine, sophocarpine, sophoridine, as well as their mixture both in distilled H2O and in the soil matrix. Our results revealed that all the alkaloids possessed inhibitory activity on four receiver species, i.e., Amaranthus retroflexus, Medicago sativa, Lolium perenne and Setaria viridis. The strength of the phytotoxicity of the alkaloids was in the following order: sophocarpine > aloperine > mixture > sophoridine > matrine > oxysophocarpine > oxymatrine (in Petri dish assays), and matrine > mixture > sophocarpine > oxymatrine > oxysophocarpine > sophoridine > aloperine (in pot experiments). In addition, the mixture of the alkaloids was found to significantly increase the IAA content, MDA content and POD activity of M. sativa seedlings, whereas CTK content, ABA content, SOD activity and CAT activity of M. sativa seedlings decreased markedly. Our results suggest S. alopecuroides might produce allelopathic alkaloids to improve its competitiveness and thus facilitate the establishment of its dominance; the potential value of these alkaloids as environmentally friendly herbicides is also discussed.

Toxins published new progress about Alfalfa. 6882-68-4 belongs to class naphthyridine, and the molecular formula is C15H24N2O, Safety of (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

Li, Jian-Chun; Dai, Wei-Feng; Liu, Dan; Zhang, Zhi-Jun; Jiang, Ming-Yan; Rao, Kai-Rui; Li, Rong-Tao; Li, Hong-Mei published the artcile< Quinolizidine alkaloids from Sophora alopecuroides with anti-inflammatory and anti-tumor properties>, 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 Sophora Quinolizidine alkaloid anti inflammatory antitumor; Anti-inflammatory; Anti-tumor; Leguminosae; Quinolizidine alkaloids; Sophora alopecuroides.

Forty-three quinolizidine alkaloids (1-43), including twelve new matrine-type ones, sophalodes A-L (1-7, 17, 19 and 28-30), were isolated from the seeds of Sophora alopecuroides. Structurally, compounds 1-4 were the first examples of C-11 oxidized matrine-type alkaloids from Sophora plants. The structures and absolute configurations of new compounds were elucidated by extensive spectroscopic techniques, X-ray diffraction anal., and quantum chem. calculation In addition, the NMR data and absolute configuration of compound 18 was reported for the first time. All the isolates were evaluated for their inhibition on nitric oxide production induced by lipopolysaccharide in RAW 264.7 macrophages, among them, compounds 29, 38 and 42 exhibited the most significant activity with IC50 values of 29.19, 25.86 and 33.30μM, resp. Further research about new compound 29 showed that it also suppressed the protein levels of iNOS and COX-2, which revealed its anti-inflammatory potential. Moreover, addnl. research showed that compound 16 exhibited marginal cytotoxicity against HeLa cell lines, with an IC50 value of 24.27μM.

Bioorganic Chemistry published new progress about Anti-HIV agents. 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

Watanabe, Tatsuro; Sato, Akemi; Kobayashi-Watanabe, Naomi; Sueoka-Aragane, Naoko; Kimura, Shinya; Sueoka, Eisaburo published the artcile< Torin2 potentiates anticancer effects on adult T-cell leukemia/lymphoma by inhibiting mammalian target of rapamycin>, Safety of 9-(6-Aminopyridin-3-yl)-1-(3-(trifluoromethyl)phenyl)benzo[h][1,6]naphthyridin-2(1H)-one, the main research area is T cell leukemia lymphoma Torin2 anticancer mTOR signaling; AKT; Adult T-cell leukemia/lymphoma; growth inhibition; mammalian target of rapamycin.

Background: Torin2 is a second-generation ATP-competitive inhibitor of the mammalian target of rapamycin (mTOR). Dysregulation of mTOR signaling pathway, consisting of mTOR complexes mTORC1 and mTORC2, is a promising therapeutic target in some human malignancies. We examined antitumor effects of Torin2 in adult T-cell leukemia/lymphoma (ATL)-related cell lines compared to those of rapamycin, a classical mTOR inhibitor. Materials and Methods: Cell growth was monitored by detecting viable cells with Cell Counting Kit-8 or trypan blue. Cell cycle was studied by flow cytometric anal. The phosphorylation status of proteins in the mTOR signaling pathway was examined by western blot anal. Results: Torin2 exhibited greater efficacy in cell growth inhibition than rapamycin, associated with a strong reduction of phosphorylated v-akt murine thymoma viral oncogene homolog (AKT) (Ser 473), that is downstream of mTORC2. Conclusion: Since mTORC2 activates AKT, Torin2 might inhibit both mTORC1 and mTORC2, resulting in stronger growth inhibition of ATL cells.

Anticancer Research published new progress about Adult T-cell leukemia. 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

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