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

Abstract

Novel 3(2<i>H</i>)-pyridazinone derivatives were designed, synthesised in satisfactory yields and evaluated in different experimental assays to assess their preliminary toxicity <i>in vivo</i> and anti-proliferative effects against HCT116 cell lines <i>in vitro</i>. <i>Artemia salina</i> 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 <i>in vivo</i> 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.