Benzoxazoles and oxazolopyridines in medicinal chemistry studies

Demmer, Charles S.; Bunch, Lennart

doi:10.1016/j.ejmech.2014.11.064

Cited by 131 publications

(82 citation statements)

References 34 publications

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“…Furthermore, TEMPO and several of its derivatives induced genotoxicity in the Ames test, the mouse lymphoma assay, and the in vitro micronucleus assay (Gallez et al 1992; Guo et al 2013; Sies and Mehlhorn 1986). One TEMPO derivative, 4-methoxy-TEMPO, is commonly employed for oxidation of alcohols, as well as in synthesis of 2-substituted benzoxazoles that are widely used as antibacterial, antifungal, antimicrobial, anti-proliferative, and antiviral agents (Chen et al 2008; Demmer and Bunch 2015). In addition, one study reported that 4-methoxy-TEMPO induced apoptosis in the tumor cells of rats bearing Yoshida sarcoma (Metodiewa et al 1999).…”

Section: Introductionmentioning

confidence: 99%

ROS generation and JNK activation contribute to 4-methoxy-TEMPO-induced cytotoxicity, autophagy, and DNA damage in HepG2 cells

et al. 2017

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4-Methoxy-TEMPO, a derivative of 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO), is a stable nitroxide radical and is generally used in organic and pharmaceutical syntheses for the oxidation of alcohols. Previously, we reported the involvement of reactive oxygen species (ROS) and c-Jun N-terminal kinases (JNK) in TEMPO-induced apoptosis in mouse L5178Y cells. In this study, we investigated 4-methoxy-TEMPO induced toxicity in human HepG2 hepatoma cells and its underlying mechanisms. Treatments with 4-methoxy-TEMPO (0.5–5 mM for 2–6 h) caused oxidative stress as demonstrated by increased intensity of the ROS indicator H2DCF-DA, decreased levels of glutathione. 4-Methoxy-TEMPO treatment also induced DNA damage as characterized by increased levels of DNA tail intensity in the Comet assay, increased phosphorylation of related proteins including γ-H2A.X, p-Chk1, and p-Chk2, and activation of MAPK signaling pathways. In addition, 4-methoxy-TEMPO also induced autophagy as demonstrated by the conversion of LC3B-I to II, decreased level of p62, and the appearance of GFP-LC3B punctae. To investigate the crosstalk between different signaling pathways, pretreatment of HepG2 with N-acetylcysteine, an ROS scavenger, attenuated 4-methoxy-TEMPO-induced DNA damage, suppressed JNK activation, and diminished autophagy induction. Furthermore, inhibiting JNK activation by a JNK-specific inhibitor, SP600125, decreased DNA damage levels induced by 4-methoxy-TEMPO. These results suggest that multiple mechanisms including ROS generation, DNA damage, and MAPK activation contribute to 4-methoxy-TEMPO-induced toxicity.

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Section: Introductionmentioning

confidence: 99%

ROS generation and JNK activation contribute to 4-methoxy-TEMPO-induced cytotoxicity, autophagy, and DNA damage in HepG2 cells

et al. 2017

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“…1 In particular, benzazoles have found broad-reaching applications as bioactive compounds in medicinal chemistry, with a range of therapeutic treatments exploiting their anti-bacterial, anti-fungal, anti-parasitic and anti-cancer properties. 2 In addition, they are key components of useful ligands 3 as well as organic semiconductors and dyes. 4 The prevalence of the benzazole motif in these applications has led the synthetic community to develop numerous methodologies for the use of benzazole containing nucleophiles for the rapid synthesis of complex heterocycles.…”

Section: Introductionmentioning

confidence: 99%

Non-bonding 1,5-S⋯O interactions govern chemo- and enantioselectivity in isothiourea-catalyzed annulations of benzazoles

et al. 2016

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“…Benzo-azole derivatives are a class of important heterocyclic compounds possessing remarkable and various biological activity12. Therefore, the in vitro cytotoxicity of obtained 2-aryl benzoxazoles and benzoimidazoles analogues against several human cancer cell lines was evaluated by classic MTT methods using paclitaxel as positive control (Table 4).…”

Section: Resultsmentioning

confidence: 99%

“…2-Arylbenzoxazoles are important heterocyclic motif widely found in bioactive molecules1, pharmaceuticals2 and natural products3. 2-Substitued benzoxazoles are also fundamental scaffolds to construct novel ligands4567 and materials89.…”

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confidence: 99%

Copper-catalyzed Direct 2-Arylation of Benzoxazoles and Benzoimidazoles with Aryl Bromides and Cytotoxicity of Products

Jia

Tian²,

Qu³

et al. 2017

Sci Rep

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An efficient copper-catalyzed direct 2-arylation of benzoxazoles and benzoimidazoles with aryl bromides is presented. The CuI/PPh3-based catalyst promotes the installation of various aryl and heteroaryl groups through a C-H activation process in good to excellent yields. The cytotoxicity of obtained 2-aryl benzoxazoles (benzoimidazoles) was also evaluated and 1-methyl-2-(naphthalen-1-yl)benzoimidazole showed potential cytotoxicity.

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Benzoxazoles and oxazolopyridines in medicinal chemistry studies

Cited by 131 publications

References 34 publications

ROS generation and JNK activation contribute to 4-methoxy-TEMPO-induced cytotoxicity, autophagy, and DNA damage in HepG2 cells

ROS generation and JNK activation contribute to 4-methoxy-TEMPO-induced cytotoxicity, autophagy, and DNA damage in HepG2 cells

Non-bonding 1,5-S⋯O interactions govern chemo- and enantioselectivity in isothiourea-catalyzed annulations of benzazoles

Copper-catalyzed Direct 2-Arylation of Benzoxazoles and Benzoimidazoles with Aryl Bromides and Cytotoxicity of Products

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