Synthesis and anti-cancer activity of naphthalimide–organylselanyl conjugates

The structure-based approach remains a valuable tool for rapid and high-throughput drug discovery and lead optimisation. In this study, we report the in-silico modelling and anticancer activity of two 1,8-napthalimide (NAP) derivatives containing organyl selanyl groups. The organylselanyl function n -octylselanyl ( n -OctSe) or phenylselanyl (PhSe) was introduced at the 6-position of a naphthalimide structure having a conserved 3-(4-( tert -butyl)phenoxy)propyl function at the imide nitrogen. The resultant naphthalimide–organylselanyl conjugates, NAP-SePh and NAP-Se( n -Oct), were characterised using various spectroscopic techniques, including FTIR, ¹H, ¹³C, ⁷⁷Se NMR and high-resolution mass spectrometry (HRMS). NAP-SePh was structurally characterised by single-crystal X-ray diffraction analysis. The anticancer potential of the NAP-SePh and NAP-Se( n -Oct) was evaluated using an in vitro cell viability assay with MDA-MB-231 triple-negative breast cancer (TNBC) cells. The IC₅₀ values for compounds NAP-SePh and NAP-Se( n -Oct) were 27.92 ± 3 µM and 23.06 ± 3 μM, respectively. Molecular docking simulations revealed that NAP-SePh and NAP-Se( n -Oct) show binding affinities of −10.39 and −8.53 kcal/mol for the (1M17) active, and −10.66 and −10.59 kcal/mol for the (4HJO) inactive conformation of the tyrosine kinase domain of the epidermal growth factor receptor (EGFR) in which erlotinib, a well-known anticancer drug, binds.