A series of novel bimolecular hybrid compounds containing isoquinoline-quinoline and indole-quinoline fragments were synthesized using a two-stage Pictet–Spengler reaction. Starting from 2‑chloro‑8-methyl-3-formylquinoline, 3,4-dimethoxyphenylethylamine, and tryptamine, intermediates were obtained via imine formation, reduction, and cyclization steps. The structures of all compounds were confirmed by IR, mass spectrometry, and detailed 1D and 2D NMR analyses. Antioxidant evaluations revealed compound 11 as the most active in DPPH (16.51 mg TE/g), CUPRAC (125.39 mg TE/g), and FRAP (14.89 mg TE/g) assays, while compound 8 showed the highest ABTS (141.03 mg TE/g) and metal chelation activity (22.99 mg EDTAE/g). The highest total antioxidant capacity was recorded for compound 7 in the phosphomolybdenum (PBD) assay, with a value of 471.41 ± 12.73 mg TE/g. Enzyme inhibition studies showed compound 7 to be the strongest AChE (2.85 mg GALAE/g) and BChE (6.38 mg GALAE/g) inhibitor, while compound 11 was the most potent against tyrosinase (67.95 mg KAE/g) and amylase (1.11 mmol ACAE/g). Cytotoxicity assessments on HeLa cells revealed that compounds 6 and 10 caused >90% reduction in viability at 200 µM, with compound 1 exhibiting the lowest IC₅₀ (43.06 ± 4.88 µM). Molecular modelling also confirmed that compound 7 showed the strongest binding to AChE and BChE, while compound 11 was most active against amylase and tyrosinase. These findings highlight several promising lead compounds for further pharmacological development. © 2026 Elsevier B.V.

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