Click Chemistry Promoted Synthesis of Isatin‐Triazole Hybrids: In Silico Molecular Docking and Cytotoxic Evaluation Against A‐549 Carcinoma Cells

ABSTRACT Molecular hybridization has emerged as a powerful strategy in drug discovery, particularly for anticancer agents. The proposed work focused on the design, synthesis, and biological evaluation of a novel series of Isatin‐1,2,3‐triazole clubbed hybrids ( 8a–j ) against lung cancer. The result of the study reveals their anticancer properties and explores molecular interactions through computational approaches. The anticancer activity of these hybrids was assessed against the human lung carcinoma A‐549 cell line using the MTT assay. Additionally, molecular docking studies were performed to check the binding affinities of 8a–j with the target PDB: 4G5J, revealing strong interactions with key amino acid residues. Among the tested compounds, 8e , 8c , 8f , 8i , and 8b exhibited the most significant antiproliferative effects, with IC 50 values ranging from 69 to 80 µg/mL, highlighting their potential as therapeutic agents for lung cancer. The synthesized compounds were characterized using 1 H NMR, 13 C NMR, LC‐MS, and IR analysis to confirm their structural integrity. Computational insights confirmed the structural stability of these compounds and elucidated their mechanisms of action. Additionally, absorption, distribution, metabolism, and excretion (ADME) analyses indicated that many of the synthesized compounds exhibited favorable drug‐like characteristics, with minimal adverse effects, emphasizing their potential for advancement as cancer therapeutic agent.