Synthesis, molecular docking, and biological investigations of new pyrazolone chalcones

Heterocyclic compounds are essential to the drug development and discovery processes. Herein, we synthesized new pyrazolone chalcones (3a-g) through the reaction of azopyrazolone (2) with different aromatic aldehydes in a basic medium. Numerous techniques including elemental analysis, ¹H-NMR, ¹³C-NMR, and FT-IR spectroscopies, were used to characterize pyrazolone chalcone derivatives. Compound 3b exhibited the highest binding energy towards YAP/TEAD protein with a value of -8.45 kcal mol^-1 in in silico studies. This observation suggested that compound 3b inhibits the YAP/TEAD Hippo signaling pathway. In addition, compound 3b offered a prospective anticancer effect against various cancer cell lines, such as HepG-2, MCF-7, and HCT-116, among the other synthesized compounds, with IC₅₀ values equal to 5.03 ± 0.4, 3.92 ± 0.2, and 6.34 ± 0.5 μM, respectively. These results validated our findings regarding the in silico suppression of the YAP/TEAD protein. Its pharmacokinetic properties were theoretically observed using ADMET. Additionally, compound 3b demonstrated a potent antioxidant scavenging action (in vitro) against DPPH free radicals. Thus, based on our findings, compound 3b may act as a potential anticancer scaffold owing to its inhibitory impact towards the YAP/TEAD-mediated Hippo signaling pathway with a safe toxic profile on normal cells.