Synthesis and biological activity evaluation of aromatic bisselenocyanate compounds

Motivated by the significant physiological activities of selenocyanate pharmacophores in biomedicine and the relative scarcity of research on diselenocyanates, this study designed and synthesized a series of novel aromatic diselenocyanate derivatives (including aniline-type 3a-3f, phenol-type 6a-6f, and biphenyl-type 8) using aniline and phenol as parent structures through aromatic ring electrophilic substitution and amide bond/ether bond bridging strategies, and systematically evaluated their biological activities. The results demonstrated that multiple compounds exhibited significant inhibitory activity against specific cancer cell lines. Among them, compound 3f showed an IC₅₀ value of 2.93 μmol/L against breast cancer MCF-7 cells, while compound 6c displayed superior IC₅₀ values compared to Cisplatin against SK-OV-3, HepG-2, and MCF-7 cells. The compounds also demonstrated excellent activity against drug-resistant bacteria MRSA/VRE (3f exhibited an MIC of 2 μg mL^-1 against MRSA, outperforming Vancomycin) and agricultural crop pathogens (citrus canker, rice bacterial leaf streak/leaf blight pathogens). Notably, compound 8 achieved sub-microgram EC₅₀ values against these phytopathogens. Structure-activity relationship analysis revealed that aniline derivatives showed better activity against breast cancer, while phenol derivatives exhibited stronger inhibition against ovarian cancer and phytopathogens. Molecular-docking studies corroborate enhanced binding stability of optimized compounds to validated biological targets. Collectively, these findings provide both mechanistic insight and lead candidates for novel antineoplastic agents and low-toxicity agricultural antimicrobials.