Synthesis, Cytotoxicity, and ADME Studies of New Compounds Containing Coumarin–Indazole–Triazole Nucleus

ABSTRACT

In this work, the preparation of novel coumarin–indazole–triazole–sulfonamide hybrids was optimized using a multi‐step route. This synthesis includes nitration, reduction, sulfonamide formation, alkylation, and CuAAC coupling. The synthesized compounds were evaluated for their antiproliferative activity against MDA‐MB‐231 triple‐negative breast cancer cells. Two intermediates, 4c and 5a , stood out for exhibiting the most significant effects, with IC ₅₀ values of 37.48 and 43.67 µM, respectively, and good selectivity for healthy cells, while the 10a‐c derivatives showed lower activity. ADME analysis confirmed that these intermediates, 4a and 5a , do indeed possess better pharmacokinetic properties than the 10a‐c triazole derivatives. Overall, the study indicates that coumarin‐based sulfonamide intermediates are attractive starting points for the development of potential antitumor agents.