Evaluation of novel nitrophenol-triazole hybrid molecules: biological screening and computational profiling

This study aimed to synthesize novel nitrophenol-triazole hybrid molecules, investigate their biological activities (cholinesterase inhibition, antioxidant, and anticancer effects), and profile them using computational methods (molecular docking, ADMET). Eight new hybrid compounds were successfully synthesized, and the crystal structures of compounds 10a and 10g were determined by single-crystal X-ray diffraction analysis. Among the obtained compounds, derivative 10e exhibited notable cholinesterase inhibitory activity with high potency and selectivity against acetylcholinesterase (AChE), demonstrating an IC₅₀ value of 1.56 µM. The compounds displayed promising antioxidant capacity, especially in terms of ABTS radical scavenging activity, with IC₅₀ values ranging narrowly from 8.01 µg/mL (10a) to 8.52 µg/mL (10d). In anticancer activity evaluations, compound 10a showed noteworthy cytotoxicity against the Caco-2 cell line with an IC₅₀ value of 1.77 µM. In silico ADMET analyses predicted that most compounds adhere to Lipinski's Rule of Five and possess a favorable profile. Molecular docking studies elucidated the binding interactions, revealing binding energies of - 10.9 kcal/mol for compound 10e with AChE and - 9.1 kcal/mol for compound 10h with BuChE.