Design, Synthesis, and Evaluation of Anti‐Tumor Activity of 5‐Bromoindole‐3‐Carboxylate Methyl Ester Derivatives

ABSTRACT In the present investigation, various methyl ester derivatives of 5‐bromoindole‐3‐carboxylic acid were designed and developed. The results of in vitro experiments indicated that most of the newly synthesized compounds displayed enhanced anti‐proliferative effects when compared to both 5‐bromoindole‐3‐carboxylic acid methyl ester and (+)‐JQ‐1. Of the evaluated compounds, L6 demonstrated the most potent inhibitory activity against MDA‐MB‐231 breast cancer cells, exhibiting an IC 50 value of 0.72 ± 0.07 µM. This represents an approximately 15‐fold increase in potency compared to 5‐bromoindole‐3‐carboxylic acid methyl ester (IC50 = 10.71 ± 0.33 µM). Mechanistic investigations revealed that L6 significantly suppressed tumor cell clonogenicity, migration, and adhesion. Furthermore, in the chicken embryo chorioallantoic membrane (CAM) model, L6 exhibited anti‐angiogenic and tumor growth inhibitory effects comparable to those of 5‐fluorouracil. This study has confirmed that through a structural modification strategy inspired by natural products, a novel lead compound with strong anti‐breast cancer activity has been identified, providing valuable reference for the development of future anti‐tumor drugs.