Synthesis and biological evaluation of new 3(2H)-pyridazinone derivatives as non-toxic anti-proliferative compounds against human colon carcinoma HCT116 cells. (1st January 2020)

• Record Type: Journal Article
• Authors: Özdemir, Zeynep; Utku, Semra; Mathew, Bijo; Carradori, Simone; Orlando, Giustino; Di Simone, Simonetta; Alagöz, Mehmet Abdullah; Özçelik, Azime Berna; Uysal, Mehtap; Ferrante, Claudio
• Is Part Of: Journal of enzyme inhibition and medicinal chemistry. Volume 35:Number 1(2020)
• Page Start: 1100
• Page End: 1109
• Publication Date: 2020-01-01
• Subjects: Serotonin -- anti-proliferative agents -- pyridazinone -- kynurenic acid -- HCT116 -- wound healing -- Artemia salina lethality test; Enzyme inhibitors -- Periodicals; Enzyme Inhibitors -- periodicals; Biochemistry -- periodicals; 572.7
• DOI: 10.1080/14756366.2020.1755670
• Languages: English
• ISSNs: 1475-6366

Abstract

Abstract: Novel 3(2 H )-pyridazinone derivatives were designed, synthesised in satisfactory yields and evaluated in different experimental assays to assess their preliminary toxicity in vivo and anti-proliferative effects against HCT116 cell lines in vitro . Artemia salina lethality test provided LC50 values >100 µg/mL for all compounds. Successive assays revealed that some compounds were endowed with a promising anti-proliferative effect against HCT116 cells, alone or stimulated by serotonin as a pro-inflammatory factor in order to mimick an inflamed model in vivo of cancer cell microenvironment. Moreover, the kinurenic acid level after treatment with these newly synthesised compounds was monitored as a marker of anti-proliferation in colon carcinoma models. The IC50 values obtained for the best-in-class compounds were comparable to that of daunorubicin as a reference drug. Conversely, these compounds were not able to counteract the spontaneous migration of human cancer HCT116 cell line in the wound healing paradigm.