Identification of NQO1 and ferrochelatase as interaction partners for neuroprotective N‐{[2‐(4‐phenyl‐piperazin‐1‐yl)‐ethyl]‐phenyl}‐arylamides. (10th April 2018)

• Record Type: Journal Article
• Authors: Rajacic, Sladjana‐Kostic; Schwall, Gerhard; Penjisevic, Jelena; Andric, Deana; Sukalovic, Vladimir; Soskic, Vukic
• Is Part Of: Chemical biology & drug design. Volume 92:Number 1(2018)
• Page Start: 1393
• Page End: 1397
• Publication Date: 2018-04-10
• Subjects: arylpiperazines -- ferrochelatase -- neuroprotection -- NQO1; Drugs -- Design -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; 615.19005
• DOI: 10.1111/cbdd.13193
• Languages: English
• ISSNs: 1747-0277

Abstract

Abstract : Affinity chromatography was used to identify potential cellular targets that are responsible for neuroprotective activity of N ‐{[2‐(4‐phenyl‐piperazin‐1‐yl)‐ethyl]‐phenyl}‐arylamides. Active and inactive representatives of N ‐{[2‐(4‐phenyl‐piperazin‐1‐yl)‐ethyl]‐phenyl}‐arylamides bearing an extended linker were synthesized and immobilized on an agarose‐based matrix. This was followed by the identification of specifically bound proteins isolated out of the whole rat brain extract. Inducible flavoprotein NAD(P)H:quinone oxidoreductase (NQO1) was identified as candidates for cellular targets. Abstract : NQO1 was identified as a part of a neuroprotective arylpiperazine interactome. This finding points to NQO1 as a cellular target for N ‐{[2‐(4‐phenyl‐piperazin‐1‐yl)‐ethyl]‐phenyl}‐arylamides that is responsible for their neuroprotective activity.