New Azo Pyrazolone Candidates: Synthesis, Molecular Docking, and In Vitro Studies

Novel pyrazolone chalcones ( 3a, b ) were synthesized and coupled with diazonium salt of different aromatic amines to create a series of novel azo pyrazolones ( 4a‐5d ). various spectroscopic data were used to confirm the structure of the prepared compounds. In addition, the mode of action of these compounds was examined in silico through molecular docking against the protein of the YAP/TEAD Hippo signaling pathway to evaluate their possible antitumor properties. Additionally, ADMET pharmacokinetic studies were investigated. Our results demonstrated that compound 4c has the highest binding energy towards the target YAP/TEAD complex protein. Further, all synthesized compounds were examined (in vitro) for their anticancer impact experimentally on a panel of cancer cell lines. Their cytotoxic effects were elucidated on the normal cell line WI38, and compound 4c demonstrated potent antitumor activity without any toxic effect compared with the reference chemotherapeutic drug (DOX). Ultimately, there was consensus regarding the in vitro experiments and the molecular docking in silico simulations. Additionally, compound 4c demonstrated potent antioxidant activity against DPPH free radicals. Consequently, our results clarified that compound 4c may find application as a pharmaceutical for cancer treatment.