Novel Glycosylated Dihydropyridine-Based Nanoformulations as EGFR Inhibitors

Novel pyrimido[4,5-b]quinoline-based glycosides were synthesized via ultrasound-assisted green protocols using vanillin and cycloalkanones. To enhance anticancer efficacy, selected derivatives were formulated with selenium nanoparticles (SeNPs). In vitro assays revealed potent cytotoxicity of SeNP-conjugates 4–9 against HCT-116 and HOS cancer cell lines (IC₅₀ < 0.006 μM and 0.012–0.023 μM, respectively), though similar activity against BJ-1 normal cells indicated poor selectivity. EGFR inhibition studies showed strong activity for 4-SeNPs, 9-SeNPs, and 5-SeNPs (IC₅₀ = 0.16, 0.25, and 0.32 μM), comparable to erlotinib (IC₅₀ = 0.17 μM). Molecular docking confirmed favorable binding energies (–11.63 to –10.30 kcal/mol) and key interactions with Met769, Lys721, and Arg817. ADME predictions suggested poor oral bioavailability and parenteral suitability. These findings highlight the potential of glycosylated SeNP hybrids as EGFR-targeted anticancer agents, while underscoring the need for improved selectivity and in vivo validation.