To explore novel and potent compounds with anticancer activity, two series of 1H-1,2,3-triazole tethered dibenzosuberane conjugates ( 5a-i and 5j-n ) were synthesized using a linear and convergent approach. The synthesized novel compounds were screened for their in vitro antiproliferative activity against HepG2 cell lines using the MTT assay to explore their binding interactions with the 5EQG protein. IC 50 values revealed that the most active combination against HepG2 cell lines was triazole tethered with an ortho chloro-substituted aryl ring ( 5g ) (IC 50 : 99.64 µg/mL). The other compounds in the series exhibited comparable cytotoxic activities against HepG2 cell lines. The results were substantiated by molecular docking studies. The majority of the compounds demonstrated high binding affinity for the active site of the targeted protein. In addition, in silico drug-likeness prediction by the ADMET method has been explored with these compounds. All synthesized novel derivatives were characterized by mass spectrometry, infrared spectroscopy, 1 H-nuclear magnetic resonance (NMR) spectroscopy, and 13 C-NMR spectroscopy.