Day: December 30, 2022

Amiodarone, Unlike Dronedarone, Activates Inflammasomes via Its Reactive Metabolites: Implications for Amiodarone Adverse Reactions was written by Kato, Ryuji;Ijiri, Yoshio;Hayashi, Tetsuya. And the article was included in Chemical Research in Toxicology in 2021.SDS of cas: 1614-12-6 This article mentions the following:

Amiodarone is a benzofuran derivative used to treat arrhythmias, but its use is limited by adverse reactions. There is evidence that some of the severe adverse reactions such as liver injury and interstitial lung disease are immune-mediated; however, details of the mechanism have not been elucidated. We tested the ability of amiodarone to induce the release of danger-associated mol. patterns (DAMPs) that activate inflammasomes. Human hepatocarcinoma functional liver cell-4 (FLC-4) cells were used for drug bioactivation, and the detection of inflammasome activation was performed with the human macrophage cell line, THP-1 cells. Amiodarone is known to be oxidized to reactive quinone metabolites. The supernatant from the incubation of amiodarone with FLC-4 cells for 7 days increased caspase-1 activity and production of IL-1β by THP-1 cells. In the supernatant of FLC-4 cells with amiodarone, the heat shock protein (HSP) 40 was significantly increased. Addition of a cytochrome P 450 inhibitor to the FLC-4 cells prevented the release of HSP40 from the FLC-4 cells and activation of THP-1 inflammasomes by the FLC-4 supernatant. These results suggested that the reactive quinone metabolites of amiodarone can cause the release of DAMPs from hepatocytes which can activate inflammasomes. Dronedarone, a safer analog of amiodarone, did not activate inflammasomes. Inflammasome activation may be an important step in the activation of the immune system by amiodarone, which in some patients, can cause immune-related adverse events. In addition, our data suggest that drugs that block the effects or the formation of IL-1β would provide better treatment of amiodarone-induced immune-related adverse reactions. In the experiment, the researchers used many compounds, for example, 1H-Benzo[d][1,2,3]triazol-1-amine (cas: 1614-12-6SDS of cas: 1614-12-6).

1H-Benzo[d][1,2,3]triazol-1-amine (cas: 1614-12-6) belongs to triazole derivatives. Triazoles exhibit substantial isomerism, depending on the positioning of the nitrogen atoms within the ring. 1,2,3-Triazoles are usually prepared following (3+2) cycloaddition protocols. A common technique for unsubstituted triazoles is the Huisgen azide-alkyne 1,3-dipolar cycloaddition: a azide and an alkyne react at high temperature to form a ring. However, the Huisgen strategy produces a mixture of isomers (typically 1,4- and 1,5-disubstituted) when used to produce substituted triazoles.SDS of cas: 1614-12-6

Referemce:
1,2,3-Triazole – Wikipedia,
Triazoles – an overview | ScienceDirect Topics

Human CYP2E1-dependent and human sulfotransferase 1A1-modulated induction of micronuclei by benzene and its hydroxylated metabolites in Chinese hamster V79-derived cells was written by Jiang, Hao;Lai, Yanmei;Hu, Keqi;Wei, Qinzhi;Liu, Yungang. And the article was included in Mutation Research, Fundamental and Molecular Mechanisms of Mutagenesis in 2014.COA of Formula: C6H6N4 This article mentions the following:

Benzene is a ubiquitous environmental pollutant and a confirmed human carcinogen, which requires metabolic activation, primarily by CYP2E1, for most of its biol. actions. Chromosome damages in benzene-exposed workers and rodents have been observed, and in their urine sulfo- and glucuronide-conjugates of phenol and hydroquinone were present. Yet, direct evidence for human CYP2E1-activated mutagenicity of benzene and the exact significance of phase II metabolism for inactivating benzene metabolites are still missing. In the present study, benzene and its oxidized metabolites (phenol, hydroquinone, catechol, 1,2,4-trihydroxybenzene and 1,4-benzoquinone) were investigated for induction of micronuclei in a V79-derived cell line genetically engineered for expression of both human CYP2E1 and human sulfotransferase (SULT) 1A1 (indicated by active micronuclei induction by 1-hydroxymethylpyrene). The results demonstrated concentration-dependent induction of micronuclei by benzene and phenol, though with lower potency or efficacy than the other metabolites. Inhibition of CYP2E1 by 1-aminobenzotriazole did not change the effect of benzoquinone, but completely abolished that of benzene and phenol, and attenuated that of the other compounds Moreover, inhibition of SULT1A1 by pentachlorophenol potentiated the effects of benzene, hydroquinone, catechol and trihydroxybenzene. Ascorbic acid, a reducing and free radical-scavenging agent, significantly lowered the effects of hydroquinone, catechol, trihydroxybenzene as well as N-nitrosodimethylamine (a known CYP2E1-dependent promutagen), with that of benzoquinone unaffected. These results suggest that in addition to activating benzene and phenol, human CYP2E1 may further convert hydroquinone, catechol and trihydroxybenzene to more genotoxic metabolites, and sulfo-conjugation of the multi-hydroxylated metabolites of benzene by human SULT1A1 may represent an important detoxifying pathway. In the experiment, the researchers used many compounds, for example, 1H-Benzo[d][1,2,3]triazol-1-amine (cas: 1614-12-6COA of Formula: C6H6N4).

1H-Benzo[d][1,2,3]triazol-1-amine (cas: 1614-12-6) belongs to triazole derivatives. Many triazoles are versatile, biologically active compounds commonly used as fungicides and plant retardants. Many triazoles have antifungal effects: the triazole antifungal drugs include fluconazole, isavuconazole, itraconazole, voriconazole, pramiconazole, ravuconazole, and posaconazole and triazole plant-protection fungicides include epoxiconazole, triadimenol, myclobutanil, propiconazole, prothioconazole, metconazole, cyproconazole, tebuconazole, flusilazole and paclobutrazol.COA of Formula: C6H6N4

Referemce:
1,2,3-Triazole – Wikipedia,
Triazoles – an overview | ScienceDirect Topics

Using improved serial blood sampling method of mice to study pharmacokinetics and drug-drug interaction. was written by Watanabe, Ayahisa;Watari, Ryosuke;Ogawa, Keiko;Shimizu, Ryosuke;Tanaka, Yukari;Takai, Nozomi;Nezasa, Ken-ichi;Yamaguchi, Yoshitaka. And the article was included in Journal of pharmaceutical sciences in 2015.COA of Formula: C6H6N4 This article mentions the following:

In pharmacokinetic evaluation of mice, using serial sampling methods rather than a terminal blood sampling method could reduce the number of animals needed and lead to more reliable data by excluding individual differences. In addition, using serial sampling methods can be valuable for evaluation of the drug-drug interaction (DDI) potential of drug candidates. In this study, we established an improved method for serially sampling the blood from one mouse by only one incision of the lateral tail vein, and investigated whether our method could be adapted to pharmacokinetic and DDI studies. After intravenous and oral administration of ibuprofen and fexofenadine (BCS class II and III), the plasma concentration and pharmacokinetic parameters were evaluated by our method and a terminal blood sampling method, with the result that both methods gave comparable results (ibuprofen: 63.8 ± 4.0% and 64.4%, fexofenadine: 6.5 ± 0.7% and 7.9%, respectively, in bioavailability). In addition, our method could be adapted to DDI study for cytochrome P450 and organic anion transporting polypeptide inhibition. These results demonstrate that our method can be useful for pharmacokinetic evaluation from the perspective of reliable data acquisition as well as easy handling and low stress to mice and improve the quality of pharmacokinetic and DDI studies. In the experiment, the researchers used many compounds, for example, 1H-Benzo[d][1,2,3]triazol-1-amine (cas: 1614-12-6COA of Formula: C6H6N4).

1H-Benzo[d][1,2,3]triazol-1-amine (cas: 1614-12-6) belongs to triazole derivatives. Triazoles are important five-member nitrogen heterocycles involved in a wide range of industrial applications such as agrochemicals, corrosion inhibitors, dyes, optical brighteners, as well as biologically active agents. Both the triazoles and their derivatives have significant biological properties including antimicrobial, antiviral, antitubercular, anticancer, anticonvulsant, analgesic, antioxidant, anti-inflammatory, and antidepressant activities.COA of Formula: C6H6N4

Referemce:
1,2,3-Triazole – Wikipedia,
Triazoles – an overview | ScienceDirect Topics

Two spin-competing manganese(II) coordination polymers exhibiting unusual multi-step magnetization jumps was written by Zhang, Wei-Xiong;Xue, Wei;Zheng, Yan-Zhen;Chen, Xiao-Ming. And the article was included in Chemical Communications (Cambridge, United Kingdom) in 2009.Electric Literature of C4H3N3O4 This article mentions the following:

Two new three-dimensional manganese(II) coordination polymers, Mn₃(tzdc)₂(H₂O)₂(NH₃)₂ and Mn₃(tzdc)₂(H₂O)₄, were assembled by 1,2,3-triazole-4,5-dicarboxylate (tzdc), showing unusual multi-step magnetization jumps at 1.8 K due to the competing interactions between the antiferromagnetic couplings with different amplitudes. The mol. structures of both complexes were determined by X-ray crystallog. In the experiment, the researchers used many compounds, for example, 1H-1,2,3-Triazole-4,5-dicarboxylic acid (cas: 4546-95-6Electric Literature of C4H3N3O4).

1H-1,2,3-Triazole-4,5-dicarboxylic acid (cas: 4546-95-6) belongs to triazole derivatives. The triazole ring is a relatively stable functional group, and the triazole bond can be used for a variety of applications, such as replacing the phosphate backbone of DNA.Triazole heterocyclic structures are found to form many weak nonbond interactions with the receptors and enzymes in biological systems.Electric Literature of C4H3N3O4

Referemce:
1,2,3-Triazole – Wikipedia,
Triazoles – an overview | ScienceDirect Topics

Complexation of different transition metals with 4-(4-carboxyphenyl)-1,2,4-triazole: Synthesis, crystal structure and hirshfeld surfaces was written by Jiang, Ye-Hao;Liu, Qing-Ling;Luo, Yang-Hui;Sun, Bai-Wang. And the article was included in Journal of Molecular Structure in 2017.Reference of 157069-48-2 This article mentions the following:

Four new complexes based on the 4-(4-carboxyphenyl)-1,2,4-triazole (Hcpt) ligand, {[Co(cpt)₂(H₂O)₄]·H₂O} (1), {[Cr(cpt)₂(H₂O)₄]·10H₂O} (2), {[Fe(cpt)₂(H₂O)₄]·10H₂O} (3), {[Zn(cpt)₂ (H₂O)₂]} (4) have been synthesized and characterized by elemental anal., single crystal x-ray diffraction and TGA. For complexes 1, 2, and 3, they almost have the same coordination mode that only one nitrogen atom of triazole are involved in the coordination, while in the complex 4, only the group COO^– participates in the coordination. In the crystal structure of 1, each structural unit[Co(cpt)₂(H₂O)₄] is linked to another by hydrogen bonding formed by the lattice water mols., thus forming a one-dimensional chain structure; In the crystal structure of 2 or 3, each structural unit[Cr(cpt)₂(H₂O)₄] or [Fe(cpt)₂(H₂O)₄] forms a two-dimensional layered structure by intermol. hydrogen bonds from the coordinated water mol. and the group COO^–. The results of TGA show that the loss of lattice water and coordinated water mols. in 1, 2 and 3 is <120°, while the loss of coordinated water mols. in 4 is at 190-260°. Hirshfeld surface shows that the N-H···O hydrogen bonding interaction plays a significant role towards the conformation of the basic structure of these complexes. In the experiment, the researchers used many compounds, for example, 4-(4H-1,2,4-Triazol-4-yl)benzoic acid (cas: 157069-48-2Reference of 157069-48-2).

4-(4H-1,2,4-Triazol-4-yl)benzoic acid (cas: 157069-48-2) belongs to triazole derivatives. Triazoles are important five-member nitrogen heterocycles involved in a wide range of industrial applications such as agrochemicals, corrosion inhibitors, dyes, optical brighteners, as well as biologically active agents. Triazole growth retardants such as uniconazole and paclobutrazol have been known to inhibit the biosynthesis of gibberellins by blocking kaurene oxidase, an P450 enzymeReference of 157069-48-2

Referemce:
1,2,3-Triazole – Wikipedia,
Triazoles – an overview | ScienceDirect Topics

Metabolic map of the antiviral drug podophyllotoxin provides insights into hepatotoxicity was written by Sun, Dongxue;Gao, Xiaoxia;Wang, Qiao;Krausz, Kristopher W.;Fang, Zhongze;Zhang, Youbo;Xie, Cen;Gonzalez, Frank J.. And the article was included in Xenobiotica in 2021.Name: 1H-Benzo[d][1,2,3]triazol-1-amine This article mentions the following:

Podophyllotoxin (POD) is a natural compound with antiviral and anticancer activities. The purpose of the present study was to determine the metabolic map of POD in vitro and in vivo. Mouse and human liver microsomes were employed to identify POD metabolites in vitro and recombinant drug-metabolizing enzymes were used to identify the mono-oxygenase enzymes involved in POD metabolism All in vitro incubation mixtures and bile samples from mice treated with POD were analyzed with ultra-performance liquid chromatog. coupled with electrospray ionization quadrupole time-of-flight mass spectrometry. A total of 38metabolites, including six phase-I metabolites and 32 phase-II metabolites, of POD were identified from bile and faeces samples after oral administration, and their structures were elucidated through interpreting MS/MS fragmentation patterns. Nine metabolites, including two phase-I metabolites, five glucuronide conjugates, and two GSH conjugates were detected in both human and mouse liver microsome incubation systems and the generation of all metabolites were NADPH-dependent. The main phase-I enzymes involved in metabolism of POD in vitro include CYP2C9, CYP2C19, CYP3A4, and CYP3A5. POD administration to mice caused hepatic and intestinal toxicity, and the cellular damage was exacerbated when 1-aminobenzotriazole, a broad-spectrum inhibitor of CYPs, was administered with POD, indicating that POD, but not its metabolites, induced hepatic and intestinal toxicities. This study elucidated the metabolic map and provides important reference basis for the safety evaluation and rational for the clin. application of POD. In the experiment, the researchers used many compounds, for example, 1H-Benzo[d][1,2,3]triazol-1-amine (cas: 1614-12-6Name: 1H-Benzo[d][1,2,3]triazol-1-amine).

1H-Benzo[d][1,2,3]triazol-1-amine (cas: 1614-12-6) belongs to triazole derivatives. The many free lone pairs in triazoles make them useful as coordination compounds, although not typically as haptic ligands. Triazoles are compounds with a vast spectrum of applications, varying from materials (polymers), agricultural chemicals, pharmaceuticals, photoactive chemicals and dyes.Name: 1H-Benzo[d][1,2,3]triazol-1-amine

Referemce:
1,2,3-Triazole – Wikipedia,
Triazoles – an overview | ScienceDirect Topics

Synthesis and antifungal activity of novel thiazole-containing triazole antifungals. II. Optically active ER-30346 and its derivatives was written by Tsuruoka, Akihiko;Kaku, Yumiko;Kakinuma, Hiroyuki;Tsukada, Itaru;Yanagisawa, Manabu;Nara, Kazumasa;Naito, Toshihiko. And the article was included in Chemical & Pharmaceutical Bulletin in 1998.HPLC of Formula: 179056-04-3 This article mentions the following:

A series of novel thiazole-containing triazole antifungals, I (R₁ = Ph, 4-FC₆H₄, Q, etc.) and II (X = CH, N, Y = Cl, F, CSNH₂, etc.), was synthesized and evaluated for antifungal activity against a variety of clin. isolated pathogenic fungi in vitro and against systemic candidosis in vivo. These compounds showed potent antifungal activities in vitro and in vivo. In particular, (2R,3R)-3-[4-(4-cyanophenyl)thiazol-2-yl]-2-(2,4-difluorophenyl)-1-(1H-1 ,2,4-triazol-1-yl)-2-butanol (ER-30346) showed potent and well-balanced in vitro activities and potent in vivo efficacy, and had a good safety profile. In the experiment, the researchers used many compounds, for example, 4-(2H-1,2,3-Triazol-2-yl)benzaldehyde (cas: 179056-04-3HPLC of Formula: 179056-04-3).

4-(2H-1,2,3-Triazol-2-yl)benzaldehyde (cas: 179056-04-3) belongs to triazole derivatives. The triazole ring is a relatively stable functional group, and the triazole bond can be used for a variety of applications, such as replacing the phosphate backbone of DNA. Many triazoles have antifungal effects: the triazole antifungal drugs include fluconazole, isavuconazole, itraconazole, voriconazole, pramiconazole, ravuconazole, and posaconazole and triazole plant-protection fungicides include epoxiconazole, triadimenol, myclobutanil, propiconazole, prothioconazole, metconazole, cyproconazole, tebuconazole, flusilazole and paclobutrazol.HPLC of Formula: 179056-04-3

Referemce:
1,2,3-Triazole – Wikipedia,
Triazoles – an overview | ScienceDirect Topics

Cyhalothrin biodegradation in Cunninghamella elegans was written by Palmer-Brown, William;de Melo Souza, Paula Leticia;Murphy, Cormac D.. And the article was included in Environmental Science and Pollution Research in 2019.Application of 1614-12-6 This article mentions the following:

The insecticide λ-cyhalothrin was incubated with planktonic and biofilm cultures of the fungus Cunninghamella elegans. ¹⁹F NMR spectroscopy demonstrated that the compound was initially biosorbed to the biomass and more slowly degraded by the fungus. Furthermore, the presence of trifluoromethyl-containing metabolites was observed Anal. of culture extracts by gas chromatog.-mass spectrometry (GC-MS) identified non-fluorinated metabolites that suggested the likely catabolic pathway. The hydroxylated metabolites were probably generated from the action of cytochromes P 450 (CYPs), as the presence of CYP inhibitors resulted in the absence of biodegradation Planktonic cells were measurably faster at degrading the pesticide compared with biofilm. In the experiment, the researchers used many compounds, for example, 1H-Benzo[d][1,2,3]triazol-1-amine (cas: 1614-12-6Application of 1614-12-6).

1H-Benzo[d][1,2,3]triazol-1-amine (cas: 1614-12-6) belongs to triazole derivatives. The triazole ring is a relatively stable functional group, and the triazole bond can be used for a variety of applications, such as replacing the phosphate backbone of DNA. The presence of the three nitrogen atoms in triazole structures afforded opportunities for a plethora of structural modification with the generation of novel therapeutically potential agents, which is different from other heterocyclic compounds.Application of 1614-12-6

Referemce:
1,2,3-Triazole – Wikipedia,
Triazoles – an overview | ScienceDirect Topics

An unprecedented Co^II cuboctahedron as the secondary building unit in a Co-based metal-organic framework was written by Holmberg, Rebecca J.;Kay, Marika;Korobkov, Ilia;Kadantsev, Eugene;Boyd, Peter G.;Aharen, Tomoko;Desgreniers, Serge;Woo, Tom K.;Murugesu, Muralee. And the article was included in Chemical Communications (Cambridge, United Kingdom) in 2014.Application In Synthesis of 4-(4H-1,2,4-Triazol-4-yl)benzoic acid This article mentions the following:

A cubic metal-organic framework, [Co^II₈(OH)₆(cpt)₆][CoCl₄]₂ (Hcpt = 4-(4′-carboxyphenyl)-1,2,4-triazole), with an unprecedented octanuclear secondary building unit (SBU) was isolated. The obtained SBU is composed of 8 Co^II ions at each vertex, 6 μ₄-OH groups at each face, and 12 cpt^– ligands framing the metal core. The cuboctahedra arrange in a ubt framework topol., eliciting a highly sym. MOF structure. Magnetic measurements as well as DFT calculations on this crystalline MOF reveal intramol. antiferromagnetic coupling between Co^II ions in the octanuclear SBU. In the experiment, the researchers used many compounds, for example, 4-(4H-1,2,4-Triazol-4-yl)benzoic acid (cas: 157069-48-2Application In Synthesis of 4-(4H-1,2,4-Triazol-4-yl)benzoic acid).

4-(4H-1,2,4-Triazol-4-yl)benzoic acid (cas: 157069-48-2) belongs to triazole derivatives. Many triazoles are versatile, biologically active compounds commonly used as fungicides and plant retardants. 1,2,3-Triazoles are usually prepared following (3+2) cycloaddition protocols. A common technique for unsubstituted triazoles is the Huisgen azide-alkyne 1,3-dipolar cycloaddition: a azide and an alkyne react at high temperature to form a ring. However, the Huisgen strategy produces a mixture of isomers (typically 1,4- and 1,5-disubstituted) when used to produce substituted triazoles.Application In Synthesis of 4-(4H-1,2,4-Triazol-4-yl)benzoic acid

Referemce:
1,2,3-Triazole – Wikipedia,
Triazoles – an overview | ScienceDirect Topics

Subtypes of sodium-dependent high-affinity L-[³H]glutamate transport activity: Pharmacologic specificity and regulation by sodium and potassium was written by Robinson, Michael B.;Sinor, Jeroo D.;Dowd, Lisa A.;Kerwin, James F. Jr.. And the article was included in Journal of Neurochemistry in 1993.Reference of 4546-95-6 This article mentions the following:

Some data suggest that sodium-dependent, high-affinity L-glutamate (Glu) transport sites in forebrain are different from those in cerebellum. In the present study, sodium-dependent transport of L-[³H]Glu was characterized in cerebellum and cortex. In both cerebellar and cortical tissue, activity was enriched in synaptosomes. Approx. 100 excitatory amino acid analogs were tested as potential inhibitors of transport activity. Many of the compounds tested inhibited transport activity by <65% at 1 mM and were not studied further. One group of compounds exhibited inhibition conforming to theor. curves with Hill coefficients of 1 and were <10-fold selective as inhibitors of transport activity. These included three of the putative endogenous substrates for transport: L-Glu, L-aspartate, and L-cysteate. Four of the compounds exhibited inhibition conforming to theor. curves with Hill coefficients of 1 and were >10-fold selective as inhibitors. These included β-N-oxalyl-L-α,β-diaminopropionate, α-methyl-DL-glutamate, (2S, 1′S, 2′S)-2-(carboxycyclopropyl)glycine, and (2S, 1′S, S, 3′S)-2-(2-carboxy-3-methoxymethylcyclopropyl)glycine. Data obtained with a few of the inhibitors were consistent with two sites in one or both of the brain regions. (2S, 1′R, 2′R)-2-(Carboxycyclopropyl)glycine (L-CCG-II) was identified as the most potent (IC₅₀ = 5.5 μM) and selective (60-100-fold) inhibitor of transport activity in the cerebellum. One of the potential endogenous substrates, L-homocysteate, was also a selective inhibitor of cerebellar transport activity. The data for inhibition of transport activity in cortex by both L-CCG-II and L-homocysteate were best fit to two sites. Kainate was equipotent as an inhibition were best fit to two sites. The possibility that there are four subtypes of excitatory amino acid transport is discussed. Altering sodium and potassium levels affects cerebellar and cortical transport activity differently, suggesting that the differences extend to other recognition sites on these transporters. In the experiment, the researchers used many compounds, for example, 1H-1,2,3-Triazole-4,5-dicarboxylic acid (cas: 4546-95-6Reference of 4546-95-6).

1H-1,2,3-Triazole-4,5-dicarboxylic acid (cas: 4546-95-6) belongs to triazole derivatives. The triazole ring is a relatively stable functional group, and the triazole bond can be used for a variety of applications, such as replacing the phosphate backbone of DNA. The presence of the three nitrogen atoms in triazole structures afforded opportunities for a plethora of structural modification with the generation of novel therapeutically potential agents, which is different from other heterocyclic compounds.Reference of 4546-95-6

Referemce:
1,2,3-Triazole – Wikipedia,
Triazoles – an overview | ScienceDirect Topics