Novel interleukin-5 inhibitors based on hydroxyethylaminomethyl-4H-chromen-4-one scaffold

Joo, Cheonik; Venkateswararao, Eeda; Lee, Ki-Cheul; Sharma, Vinay K.; Kyung, Min-Sik; Kim, Youngsoo; Jung, Sang‐Hun

doi:10.1016/j.bmc.2012.08.006

Cited by 13 publications

(9 citation statements)

References 18 publications

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“…It is important that in one case we found that the IL-6 inhibition in terms of mechanism of action is supported by the antioxidant activity of the compounds (Equation 16). …”

Section: Sar and Qsar In Environmental Research 953mentioning

confidence: 97%

“…Jung et al [16], continuing their research, synthesized a series of derivatives bearing the hydroxyethylaminomethyl-4H-chromen-4-one scaffold in order to establish structure-activity relationships and to identify the important features for interleukin-5 inhibition. The following equation (Equation 7) was obtained by using the IC 50 values (Table 3): Table 3.…”

Section: Hydroxyethylaminomethyl-4h-chromen-4-onesmentioning

confidence: 99%

“…Table 11. Structures, biological data [30] and physiochemical parameters used to obtain Equation (16). …”

Section: -Amino-3-heteroaryl-quinoxalinesmentioning

confidence: 99%

“…The following equation (Equation 7) was obtained by using the IC 50 values (Table 3): Table 3. Structures, biological data [16] and physiochemical parameters used to obtain Equation (7). (Table 3) some data were not included in our analysis.…”

Section: Hydroxyethylaminomethyl-4h-chromen-4-onesmentioning

confidence: 99%

“…Although corticosteroids are established immunosuppressive agents, their action is not selective and they cause metabolic and endocrinal side effects [9], whereas compounds with IL-5 inhibitory activity act selectively in reducing eosinophilic inflammation. In the literature small molecules are referred as IL-5 inhibitors (Figure 1): chalcones [10,11], isothiazolones through modification of Cys66 (Cysteine66) in IL-5Ra (interleukin 5 receptor subunit alpha) [12], isoflavonones as sophoricoside analogues [13,14], hydroxyalkylaminomethylchromones [15], derivatives based on hydroxyethylaminomethyl-4H-chromen-4-one scaffold [16], chromone analogues [17], isoflavones and aurones [18]. Mepolizumab and reslizumab, two monoclonal anti-IL-5 antibodies, and benralizumab, a monoclonal antibody directed at the IL-5 receptor, have been tested in clinical trials for the treatment of bronchial asthma, nasal polyposis, atopic dermatitis, eosinophilic oesophagitis, hypereosinophilic syndrome and Churg-Strauss syndrome [19].…”

Section: Introductionmentioning

confidence: 99%

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Cytokines in terms of QSAR. Review, evaluation and comparative studies

Konstantinidou

Hadjipavlou‐Litina

2013

SAR and QSAR in Environmental Research

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Cytokines represent a class of chemical factors that act as mediators in the complex biological response of inflammation, potentially implicated in various diseases. Therefore, selective inhibition or antagonism of cytokines is a target of anti-inflammatory drug design. The QSAR (Quantitative Structure-Activity Relationships) analysis presented here attempts to identify the structural features and physicochemical properties that are significant for cytokine antagonists or inhibitors and in particular of i) interleukin-5 (IL-5), ii) interleukin-6 (IL-6) and iii) of the chemotactic cytokine (chemokine) interleukin-8 (IL-8). Firstly, a historical aspect of the limited published QSARs is discussed and then a 2D-QSAR analysis was carried out for 26 data sets of compounds using the C-QSAR program of Biobyte. In six cases hydrophobicity appeared to be important. Steric factors in the form of overall molar refractivity (CMR), molar refractivity of the substituent (MR), molar volume (MgVol), Taft's Es constant and the sterimol parameters B1 and B5 have a significant impact on biological activity in most of the derived equations whereas electronic parameters as σp, σm or Σσ appeared in five cases.

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“…It is important that in one case we found that the IL-6 inhibition in terms of mechanism of action is supported by the antioxidant activity of the compounds (Equation 16). …”

Section: Sar and Qsar In Environmental Research 953mentioning

confidence: 97%

Section: Hydroxyethylaminomethyl-4h-chromen-4-onesmentioning

confidence: 99%

“…Table 11. Structures, biological data [30] and physiochemical parameters used to obtain Equation (16). …”

Section: -Amino-3-heteroaryl-quinoxalinesmentioning

confidence: 99%

Section: Hydroxyethylaminomethyl-4h-chromen-4-onesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Cytokines in terms of QSAR. Review, evaluation and comparative studies

Konstantinidou

Hadjipavlou‐Litina

2013

SAR and QSAR in Environmental Research

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Chromones: A Promising Ring System for New Anti‐inflammatory Drugs

2016

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The quest for safer anti-inflammatory drugs is still the focus of several medicinal chemistry programs. Chromones (4H-chromen-4-ones) are a group of naturally occurring compounds ubiquitous in plants, and the chromone core has proven to be a privileged scaffold in medicinal chemistry. Herein we provide an overview of the relevance of chromones as anti-inflammatory agents, specifically as inhibitors of cyclooxygenase (COX), 5-lipoxygenase (5-LOX), interleukin-5 (IL-5), and nitric oxide ( NO) production. Numerous structure-activity relationships and mechanisms of action are discussed. This review is therefore intended to provide a foundation for the design and synthesis of novel chromone-based compound libraries for further development into safer and more efficient anti-inflammatory agents.

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