Design, synthesis and mechanistic anticancer activity of new acetylated 5-aminosalicylate-thiazolinone hybrid derivatives.

The development of hybrid compounds has been widely considered as a promising strategy to circumvent the difficulties that emerge in cancer treatment. The well-established strategy of adding acetyl groups to certain drugs has been demonstrated to enhance their therapeutic efficacy. Based on our previous work, an approach of accommodating two chemical entities into a single structure was implemented to synthesize new acetylated hybrids ( and ) from 5-aminosalicylic acid and 4-thiazolinone derivatives. These acetylated hybrids showed potential anticancer activities and distinct metabolomic profile with antiproliferative properties. The molecular docking predicts a strong binding of and to cell cycle regulators, and transcriptomic analysis revealed DNA repair and cell cycle as the main targets of compounds. These findings were validated using models. In conclusion, the pleiotropic biological effects of and compounds on cancer cells demonstrated a new avenue to develop more potent cancer therapies.