Synthesis of bicyclo[5.3.0]azulene derivatives

Nolting, Donald D.; Nickels, Michael L.; Price, Ronald R.; Gore, John C.; Pham, Wellington

doi:10.1038/nprot.2009.99

Cited by 8 publications

(4 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We synthesized 2-methyl azulene 2 and reported that outcome in previous publications (Pham et al, 2002; Nolting et al, 2009). All reagents were obtained through commercial sources such as Sigma–Aldrich, Acros, or Tokyo Chemical Industry (TCI) and were used without further purification.…”

Section: Methodsmentioning

confidence: 89%

See 1 more Smart Citation

Convergent synthesis and evaluation of 18F-labeled azulenic COX2 probes for cancer imaging

Nolting¹,

Nickels²,

Tantawy³

et al. 2013

Front. Oncol.

Self Cite

View full text Add to dashboard Cite

The overall objectives of this research are to (i) develop azulene-based positron emission tomography (PET) probes and (ii) image COX2 as a potential biomarker of breast cancer. Several lines of research have demonstrated that COX2 is overexpressed in breast cancer and that its presence correlates with poor prognoses. While other studies have reported that COX2 inhibition can be modulated and used beneficially as a chemopreventive strategy in cancer, no viable mechanism for achieving that approach has yet been developed. This shortfall could be circumvented through in vivo imaging of COX2 activity, particularly using sensitive imaging techniques such as PET. Toward that goal, our laboratory focuses on the development of novel 18F-labled COX2 probes. We began the synthesis of the probes by transforming tropolone into a lactone, which was subjected to an [8 + 2] cycloaddition reaction to yield 2-methylazulene as the core ring of the probe. After exploring numerous synthetic routes, the final target molecule and precursor PET compounds were prepared successfully using convergent synthesis. Conventional 18F labeling methods caused precursor decomposition, which prompted us to hypothesize that the acidic protons of the methylene moiety between the azulene and thiazole rings were readily abstracted by a strong base such as potassium carbonate. Ultimately, this caused the precursors to disintegrate. This observation was supported after successfully using an 18F labeling strategy that employed a much milder phosphate buffer. The 18F-labeled COX2 probe was tested in a breast cancer xenograft mouse model. The data obtained via successive whole-body PET/CT scans indicated probe accumulation and retention in the tumor. Overall, the probe was stable in vivo and no defluorination was observed. A biodistribution study and Western blot analysis corroborate with the imaging data. In conclusion, this novel COX2 PET probe was shown to be a promising agent for cancer imaging and deserves further investigation.

show abstract

Section: Methodsmentioning

confidence: 89%

“…Of note, we synthesized the main azulene ring using the procedure we reported previously (Pham et al, 2002; Nolting et al, 2009). The two other ring structures were assembled onto the azulene ring using commercially available analogs.…”

Section: Introductionmentioning

confidence: 99%

Convergent synthesis and evaluation of 18F-labeled azulenic COX2 probes for cancer imaging

Nolting¹,

Nickels²,

Tantawy³

et al. 2013

Front. Oncol.

Self Cite

View full text Add to dashboard Cite

show abstract

“…In addition, these effects might cause a great influence on the optical and electrochemical properties to the 1-AzTCBDs and 1-AzDCNQs and might improve the redox stability on the spectroelectrochemical experiments. Therefore, we decided to bring the 2-methyl-1-azulenyl (2-Me-1-Az) group into TCBDs and DCNQs for the model derivatives with the substituent at the 2-position, since the 2-methylazulene precursors can be readily prepared in high yields and might induce the steric congestion around the TCBD and DCNQ moieties that affect their electrochromic behavior …”

Section: Introductionmentioning

confidence: 99%

Synthesis of 2-Methyl-1-azulenyl Tetracyanobutadienes and Dicyanoquinodimethanes: Substituent Effect of 2-Methyl Moiety on the Azulene Ring toward the Optical and Electrochemical Properties

et al. 2018

View full text Add to dashboard Cite

We describe the comparative study of optical and electrochemical properties of tetracyanobutadienes (TCBDs) and dicyanoquinodimethanes (DCNQs) with a 2-methyl-1-azulenyl group and their derivatives with a 1-azulenyl substituent examined under the same conditions. TCBDs and DCNQs with a 2-methyl-1-azulenyl substituent have been prepared by the Sonogashira-Hagihara alkynylation of the 2-methyl-1-iodoazulene with arylalkyne derivatives, followed by the formal [2+2] cycloaddition-retroelectrocyclization (CA-RE) reaction with tetracyanoethylene and 7,7,8,8-tetracyanoquinodimethane. The optical properties of the TCBDs and DCNQs with a 2-methyl-1-azulenyl group were investigated through the comparison with those of TCBDs and DCNQs with a 1-azulenyl substituent by employing the UV/vis spectroscopy and theoretical calculations. The electrochemical properties of the TCBD and DCNQ derivatives were also examined by cyclic voltammetry and differential pulse voltammetry experiments, which elucidated their multistep redox properties. Furthermore, noticeable spectral changes of these chromophores were identified by the spectroelectrochemical measurements.

show abstract

“…To be mentioned, Azulene is one of the main components in MCEO, which has been recognized for its application in medicinal therapy against inflammation. 58,59 Azulene is one of these compounds whose anti-inflammatory potential have been shown by the previous studies, but a detailed analysis of its effect at the cellular level in terms of proinflammatory cytokine production has not been studied yet. In the following experiments, we will investigate the anti-inflammatory effect of Azulene on HaCaT cells in vitro and on IMQ-induced psoriatic-like skin inflammation.…”

mentioning

confidence: 99%

Essential Oil of Matricaria chamomilla Alleviate Psoriatic-Like Skin Inflammation by Inhibiting PI3K/Akt/mTOR and p38MAPK Signaling Pathway

Chen,

Lv,

Nie

et al. 2024

CCID

View full text Add to dashboard Cite

Background:The traditional Matricaria chamomilla L. has been used to treat dermatitis for thousands of years. Due to emerging trends in alternative medicine, patients prefer natural remedies to relieve their symptoms. Therefore, finding safe and effective plant medicines for topical applications on the skin is an important treatment strategy for dermatologists. German chamomile (Matricaria chamomilla L.) from the Compositae family is a famous medicinal plant, often known as the "star of medicinal species."However, the function of Matricaria chamomilla essential oil on skin inflammation has not been thoroughly examined in earlier research. Methods: GC-MS analyzed the components of MCEO, and this study explored the anti-inflammation effects of MCEO on psoriasis with network pharmacological pathway prediction. Following this, we used clinical samples of psoriasis patients to confirm the secretory characteristic of relative inflammatory markers. The therapeutic effect of MCEO on skin inflammation was detected by examination of human keratinocytes HaCaT. At the same time, we prepared imiquimod-induced psoriatic-like skin inflammation in mice to investigate thoroughly the potential inhibition functions of MCEO on psoriatic skin injury and inflammation. Results: MCEO significantly reduced interleukin-22/tumor necrosis factor α/lipopolysaccharide-stimulated elevation of HaCaT cell inflammation, which was correlated with downregulating PI3K/Akt/mTOR and p38MAPK pathways activation mediated by MCEO in HaCaT cells treated with IL-22/TNF-α/LPS. Skin inflammation was evaluated based on the PASI score, HE staining, and relative inflammatory cytokine levels. The results showed that MCEO could significantly contribute to inflammatory skin disease treatment. Conclusion: MCEO inhibited inflammation in HaCaT keratinocytes induced by IL-22/TNF-α/LPS, the potential mechanisms associated with inhibiting excessive activation and crosstalk between PI3K/Akt/mTOR and p38MAPK pathways. MCEO ameliorated skin injury in IMQ-induced psoriatic-like skin inflammation of mice by downregulating the levels of inflammatory cytokines but not IL-17A. Thus, anti-inflammatory plant drugs with different targets with combined applications were a potential therapeutic strategy in psoriasis.

show abstract

Synthesis of bicyclo[5.3.0]azulene derivatives

Cited by 8 publications

References 20 publications

Convergent synthesis and evaluation of 18F-labeled azulenic COX2 probes for cancer imaging

Convergent synthesis and evaluation of 18F-labeled azulenic COX2 probes for cancer imaging

Synthesis of 2-Methyl-1-azulenyl Tetracyanobutadienes and Dicyanoquinodimethanes: Substituent Effect of 2-Methyl Moiety on the Azulene Ring toward the Optical and Electrochemical Properties

Essential Oil of Matricaria chamomilla Alleviate Psoriatic-Like Skin Inflammation by Inhibiting PI3K/Akt/mTOR and p38MAPK Signaling Pathway

Contact Info

Product

Resources

About