Synthesis, characterization and evaluation of novel isoquinoline analogues as anticancer agents

•Synthesis and characterisation of novel tetrahydrobenz[f]isoquinoles.•In-vitro cell viability assay using methotrexate as a standard drug•Molecular docking studies•In silico anti-cancer and ADMET assessment A facile synthetic strategy is reported forthe preparation of divergent 2-(1,2-dihydro-9-methoxy-4-methylbenzo[f]isoquinolin-3(4H)-yl)-N-phenylacetamides (12a-l), 1-(4-(3-trifluoromethyl)-phenyl)piperazin-1-yl)-2-(1,2-dihydro-9-methoxy-4-methylbenzo[f]isoquinolin-3-(4H) -yl)ethanones (13a-c)and 1-(2-(1,2-dihydro-9-methoxy-4-methyl benzo[f]isoquinolin-3-(4H)-yl)acetyl)indoline-5-carbonitriles (14a-c) in good yield using 1,2,3,4-Tetrahydro-9-methoxy-4-alkyl/arylbenzo [f]isoquinolines (5a-c) as the key intermediate starting from 2-(2-methoxynaphthalen-8-yl)-ethanamine (1) and acid chloride (2a-c). All the synthesised compounds were purified and characterised by IR, 1H, 13C NMR and Mass spectral data analysis. The final products 12a-l, 13a-c and 14a-c were screened for preliminary anticancer activity and ADMET assessment. All the compounds under investigation exhibited reasonably good ADMET values and moderate to good anti-cancer activities. [Display omitted]