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


ÖZDEMİR Z., UTKU S., Mathew B., Carradori S., Orlando G., Di Simone S., ...More

JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY, vol.35, no.1, pp.1100-1109, 2020 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 35 Issue: 1
  • Publication Date: 2020
  • Doi Number: 10.1080/14756366.2020.1755670
  • Journal Name: JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, BIOSIS, EMBASE, Food Science & Technology Abstracts, MEDLINE, Directory of Open Access Journals
  • Page Numbers: pp.1100-1109
  • Erzincan Binali Yildirim University Affiliated: No

Abstract

Novel 3(2H)-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 mu g/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.