Nano catalyzed green synthesis of chalcone derivatives and its anti-oxidant and anti-lung cancer potential validated through in vitro experimentals, in silico quantum chemical, molecular docking and simulation studies.

UNLABELLED: Using nanocatalysts Al(OH)₃ and Ti/Fe@Al(OH)₃ through the green chemical method, a number of new adamantyl-substituted quinoline-based chalcone derivatives (CD1 to CD9) have been synthesized. The synthesized compounds were evaluated for anti-cancer potential and anti-oxidant activity. Moreover, these chalcone derivatives have shown excellent antioxidant potential with IC50 values in the range of 18.20 µg/ml to 23.10 µg/ml. CD1 to 9 (CD1 to CD9) were subjected to in-silico screening of anti-cancer potential against lung cancer through a series of assays. Drug likeness analysis results revealed that chalcone derivatives CD5, CD8, and CD9 and reference standard drugs lorlatinib and topotecan showed no violations against all five drug likeness rules. Molecular docking analysis of CD1 to CD9 against five lung cancer target proteins revealed that binding affinity was in the range of -7.1 to -10.7 kcal/mol. In that CD5 compound, exhibit the highest docking score of -10.7 kcal/mol through three hydrogen-bonded (His188, Ser194, Gly210) and five non-bonded (Leu74, Val82, Ala95, Met143, Leu197) interactions at the binding pockets. Bioactivity analysis results revealed that chalcone derivatives CD1 to CD9 are moderately active against the enzyme channel and inhibitor. A better pharmacokinetic profile was exhibited by chalcone derivatives than the reference standard drug. MD simulation between chalcone derivatives and lung cancer target protein exhibits an excellent simulation trajectory, which was further confirmed by the MMGBA score than the reference standard drug molecule. The development of effective anticancer chalcone derivatives faces challenges such as low synthetic efficiency, harsh reaction conditions, and limited target specificity. Conventional methods often produce low yields and require extensive purification, while multi-target activity and pharmacokinetic optimization remain bottlenecks. Current study overcomes these challenges by employing green nanocatalysts (Al(OH)₃ and Ti/Fe@Al(OH)₃) for eco-friendly, high-yield synthesis and computational screening to design potent, multi-target lung cancer therapeutic chalcone compounds. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40203-026-00599-3.