Design, Synthesis, and Pharmacological Assessment of Coumarin‐Based Triazole–Phenyl Hybrids: Anticancer, Antioxidant, Antimicrobial, and In Silico Investigations

ABSTRACT Two novel libraries of coumarin‐based triazole–phenyl hybrids were efficiently synthesized via a facile, high‐yielding click chemistry approach using a 5‐chloro‐1‐pentyne linker. The synthesized derivatives were characterized by standard spectroscopic and analytical methods and evaluated for anticancer, antioxidant, and antimicrobial activities. The compound bearing a 4‐OCH 3 group ( 5c ) showed the most potent cytotoxicity against A549 lung cancer cells (IC 50 = 17.9 µM), whereas the 4‐F derivative ( 4d ) exhibited the highest antioxidant potential (2,2‐diphenyl‐1‐picrylhydrazyl [DPPH] IC 50 = 93.6 µM). The 4‐Br substituted compound ( 4f ) demonstrated broad‐spectrum antibacterial efficacy, producing the largest inhibition zones against Escherichia coli (13.67 ± 0.49 mm), Pseudomonas aeruginosa (12.33 ± 0.47 mm), Bacillus cereus (12.00 ± 0.58 mm), and Staphylococcus aureus (11.33 ± 0.61 mm). The findings verify a significant correlation between diffusion‐ and dilution‐based assays, supporting their complementary insights into antibacterial effectiveness. Additionally, the 4‐Cl derivative ( 5e ) presented considerable antifungal activity against Aspergillus niger (13.0 ± 0.8 mm). Molecular docking studies of the most active compounds revealed strong interactions with the active sites of their corresponding receptor proteins, exhibiting higher binding affinities than the reference compounds. Absorption, distribution, metabolism, excretion, and toxicity (ADMET) profiling and DFT studies (HOMO–LUMO SSgap: 3.371–4.834 eV) further supported their potential as promising pharmaceutical leads.