A comparative study for two derivatives of iodine-131-maleanilic acid: preparation, biological evaluation, docking,...

In the present study, para-methoxyphenylmaleanilic acid (MPMA) and para-fluorophenylmaleanilic acid (FPMA) were synthesized via a solvent-free approach, radiolabeled with iodine-131, and evaluated as potential dual-action chemoradiotherapeutic agents. The synthesized compounds were characterized by FT-IR spectroscopy and NMR. The radiolabeling conditions were optimized by investigating the effects of substrate concentration, pH, and oxidizing agent content. The anticancer activity of the non-radiolabeled and radiolabeled derivatives was assessed against SP2/0, MCF-7, and HepG2 cancer cell lines using MTT and apoptosis assays. In addition, molecular docking studies against the p53 Y220C mutant protein and 10 ns molecular dynamics simulations were performed to investigate binding affinity and complex stability. The results demonstrated successful radiolabeling of both derivatives, with radiochemical yields reaching 97.6% for FPMA and 93.5% for MPMA under optimized conditions. These findings demonstrate that iodine-131 labeling significantly enhances the anticancer potential of phenyl maleanilic acid derivatives, highlighting ¹³¹I-FPMA as the most promising candidate for further development as a targeted chemoradiotherapeutic agent for both hematological and solid malignancies.