Design and synthesis of aza-flavones as a new class of xanthine oxidase inhibitors

Rajni Dhiman, Sahil Sharma, Gagandip Singh, Kunal Nepali, Preet Mohinder Singh Bedi

研究成果: 雜誌貢獻文章同行評審

55 引文 斯高帕斯(Scopus)

摘要

In an attempt to develop non-purine-based xanthine oxidase (XO) inhibitors, keeping in view the complications reported with the use of purine-based XO inhibitors, the flavone framework (a class possessing XO inhibitory potential) was used as lead structure for further optimization. By means of structure-based classical bioisosterism, quinolone was used as an isoster for chromone (a bicyclic unit present in flavones), owing to the bioactive potential and drug-like properties of quinolones. This type of replacement does not alter the shape and structural features required for XO inhibition, and also provides some additional interaction sites, without the loss of hydrogen bonding and hydrophobic and arene-arene interactions. In the present study, a series of 2-aryl/heteroaryl-4-quinolones (aza analogs of flavones) was rationally designed, synthesized and evaluated for in vitro XO inhibitory activity. Some notions about structure-activity relationships are presented indicating the influence of the nature of the 2-aryl ring on the inhibitory activity. Important interactions of the most active compound 3l (IC50 = 6.24 μM) with the amino acid residues of the active site of XO were figured out by molecular modeling. To develop non-purine-based xanthine oxidase inhibitors, the flavone framework was used as lead structure for further optimization. By means of structure-based classical bioisosterism, quinolone was used as an isoster for chromone. This type of replacement does not alter the shape and structural features required for xanthine oxidase inhibition. The rationally designed and synthesized series of 2-aryl/heteroaryl-4-quinolones (aza analogs of flavones) was evaluated for in vitro xanthine oxidase inhibitory activity.
原文英語
頁(從 - 到)7-16
頁數10
期刊Archiv der Pharmazie
346
發行號1
DOIs
出版狀態已發佈 - 1月 1 2013
對外發佈

ASJC Scopus subject areas

  • 藥學科學
  • 藥物發現

指紋

深入研究「Design and synthesis of aza-flavones as a new class of xanthine oxidase inhibitors」主題。共同形成了獨特的指紋。

引用此