1,4-Disubstituted-1,2,3-triazole Linked Cyclic Ketones Ascytotoxic Agents

A series of 1,2,3-triazole-linked cyclic ketones (AR 1-14) were synthesized involving the condensation of triazole-aldehydes with cyclic ketones in tetrahydrofuran (THF) and potassium hydroxide (KOH). The synthesized derivatives were evaluated for their in-vitro cytotoxicity against retinal (hTERT RPE-1)-1), pancreatic (Capan-1), myeloid (K-562, Hap-1), colorectal (HCT 116), lung (NCI-H460), lymphoblastic (DND-41), and non-Hodgkin lymphoma (Z-138) cells. Among the tested derivatives, molecule 2,6-bis(4-((1-(4-fluorobenzyl)-1H-1,2,3-triazol-4-yl)methoxy)benzylidene)cyclohexanone (AR-7) exhibited moderate cytotoxic property with an IC₅₀ of 11.8 µM and 13.6 µM against pancreatic adenocarcinoma and colorectal carcinoma cells respectively. Molecular docking against galectin-1 receptor (PDB ID: 4Y24) demonstrated a favourable binding interaction (-7.1 kcal/mol) indicating a strong receptor-ligand affinity.