Category: naphthyridine

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

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

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

Vogel, K. R.; Ainslie, G. R.; Jansen, E. E. W.; Salomons, G. S.; Gibson, K. M. published the artcile< Therapeutic relevance of mTOR inhibition in murine succinate semialdehyde dehydrogenase deficiency (SSADHD), a disorder of GABA metabolism>, Name: 9-(6-Aminopyridin-3-yl)-1-(3-(trifluoromethyl)phenyl)benzo[h][1,6]naphthyridin-2(1H)-one, the main research area is torin mTOR succinate semialdehyde dehydrogenase deficiency GABA oxidataive stress; GABA; Oxidative stress; Succinic semialdehyde dehydrogenase deficiency; Torin 1; Torin 2; mTOR.

Aldehyde dehydrogenase 5a1-deficient (aldh5a1-/-) mice, the murine orthologue of human succinic semialdehyde dehydrogenase deficiency (SSADHD), manifest increased GABA (4-aminobutyric acid) that disrupts autophagy, increases mitochondria number, and induces oxidative stress, all mitigated with the mTOR (mechanistic target of rapamycin) inhibitor rapamycin [1]. Because GABA regulates mTOR, we tested the hypothesis that aldh5a1-/- mice would show altered levels of mRNA for genes associated with mTOR signaling and oxidative stress that could be mitigated by inhibiting mTOR. We observed that multiple metabolites associated with GABA metabolism (γ-hydroxybutyrate, succinic semialdehyde, D-2-hydroxyglutarate, 4,5-dihydrohexanoate) and oxidative stress were significantly increased in multiple tissues derived from aldh5a1-/- mice. These metabolic perturbations were associated with decreased levels of reduced glutathione (GSH) in brain and liver of aldh5a1-/- mice, as well as increased levels of adducts of the lipid peroxidation byproduct, 4-hydroxy-2-nonenal (4-HNE). Decreased liver mRNA levels for multiple genes associated with mTOR signaling and oxidative stress parameters were detected in aldh5a1-/- mice, and several were significantly improved with the administration of mTOR inhibitors (Torin 1/Torin 2). Western blot anal. of selected proteins corresponding to oxidative stress transcripts (glutathione transferase, superoxide dismutase, peroxiredoxin 1) confirmed gene expression findings. Our data provide addnl. preclin. evidence for the potential therapeutic efficacy of mTOR inhibitors in SSADHD.

Biochimica et Biophysica Acta, Molecular Basis of Disease published new progress about Animal gene Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 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

Li, Yanchu; Chen, Lu; Pu, Rong; Zhou, Lu; Zhou, Xufeng; Li, Xianyong published the artcile< Effects of a Matrine- and Sophoridine-Containing Herbal Compound Medicine (AH-05) on Liver Cancer>, Computed Properties of 6882-68-4, the main research area is liver cancer matrine sophoridine AH05.

Herbal medicine can present an alternative way of treating liver cancer. Here, we explored a matrine- and sophoridine-containing herbal compound medicine (AH-05) extracted from Adenophora capillaris, Sophora flavescens, Astragalus, and other plants. H22 and HepG2 cell models, as well as an H22 xenograft model, were established. Cell proliferation and apoptosis were measured in vitro, and tumor volume and weight were observed in vivo. The activation of AKT/mTOR and nuclear factor-κB (NF-κB) pathways in tumor cells and the polarization of CD4/CD8 T cells in the spleen were tested. To assess safety, hematol. toxicity and pathol. of the liver, kidney, spleen, and intestine were evaluated. AH-05 inhibited cell viability in a dose- and time-dependent manner. In vivo, tumor volume and weight were reduced, and the activation of NF-κB p50, NF-κB p65, AKT, p-AKT Ser473, and mTOR was suppressed. In addition, AH-05 promoted CD4+ T cell polarization in the spleen. With regard to safety, slight intestinal mucosa edema was observed, but no severe pathol. or hematol. toxicity was detected. AH-05 exhibited its therapeutic effects against liver cancer by regulating the AKT/mTOR and NF-κB signaling pathways, and the immune environment, by promoting CD4+ T cell polarization in the spleen. Thus, AH-05 represents a potential supplementary herbal compound medicine for liver cancer.

Natural Product Communications published new progress about Apoptosis. 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

Liang, Jinping; Liu, Juntong; Tang, Yezhen; Peng, Qian; Zhang, Ling; Ma, Xiaoxia; Xu, Nan; Wei, Jun; Han, Huaiqin published the artcile< Sophoridine inhibits endotoxin-induced acute lung injury by enhancing autophagy of macrophage and reducing inflammation>, Formula: C15H24N2O, the main research area is sophoridine macrophage autophagy inflammation acute lung injury; acute lung injury; autophagy; inflammation; sophoridine.

Acute lung injury (ALI) is characterized by uncontrolled inflammation, which can lead to respiratory distress syndrome and cause patient death. In this study, we sought to determine the role of sophoridine, a compound purified from sophora, in ALI. A mouse model of ALI was established by treating mice with LPS through nonexposed tracheal instillation. After LPS-induced mice were treated with sophoridine, LPS-induced alveolar wall thickening, alveolar interstitial inflammatory exudation and thickening, and the degree of pulmonary edema were found to be inhibited. Macrophages play an important role in inflammation, and in vitro experiments have demonstrated that sophoridine reduces the LPS-induced expression of inflammatory factors by macrophages, suggesting that sophoridine may inhibit lung inflammation in LPS-treated mice through reduces the secretion of inflammatory factors. Further, treatment with sophoridine up-regulated autophagy in macrophage cells in vitro and mouse lung tissues in vivo. LPS can bind to TLRs and activate the MyD88/NF-κB pathways, leading to increased inflammation in the pathogenesis of ALI. Our findings revealed that sophoridine down-regulated the expression of TLR4/MyD88/NF-κB and mTOR mRNA and protein in mouse pulmonary tissue. Collectively, these findings indicate that sophoridine may inhibit LPS-induced ALI by enhancing autophagy of macrophages and reducing inflammation.

Journal of Leukocyte Biology published new progress about Acute pulmonary injury. 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