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

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Özdemir Z., Utku S., Mathew B., Carradori S., Orlando G., Di Simone S., ...Daha Fazla

JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY, cilt.35, sa.1, ss.1100-1109, 2020 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 35 Sayı: 1
  • Basım Tarihi: 2020
  • Doi Numarası: 10.1080/14756366.2020.1755670
  • Dergi Adı: JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, BIOSIS, EMBASE, Food Science & Technology Abstracts, MEDLINE, Directory of Open Access Journals
  • Sayfa Sayıları: ss.1100-1109
  • Anahtar Kelimeler: Serotonin, anti-proliferative agents, pyridazinone, kynurenic acid, HCT116, wound healing, Artemia salina lethality test, KYNURENIC ACID, PYRIDAZINONE, ACETYLCHOLINESTERASE, PROLIFERATION
  • Gazi Üniversitesi Adresli: Evet

Özet

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.