Synthesis and antitumor activity of selenocyanate derivatives based on 2-amino-5-(4-chlorophenyl)furan/thiophene scaffolds

In this study, 2-amino-5-(4-chlorophenyl)furan/thiophene were synthesized <i>via</i> Paal-Knorr and Gewald cyclization strategies. A series of novel furan/thiophene selenocyanate derivatives were constructed by introducing selenocyanate groups with varying chain lengths through amide bonds. All compounds were structurally characterized using NMR and HR-MS analyses. MTT assay for antitumor activity revealed that several compounds exhibited superior efficacy compared to cisplatin. Notably, furan selenocyanate <b>5c</b> showed significant inhibitory activity against HepG-2 cells (IC₅₀ = 8.64 ± 0.94 μM), while thiophene selenocyanate <b>11d</b> demonstrated remarkable inhibition against HeLa and MCF-7 cells with IC₅₀ values of 6.39 and 6.77 μM, respectively. Structure-activity relationship (SAR) analysis indicated that the carbon chain length significantly influenced antitumor activity, with the C₈-chain thiophene selenocyanate derivative <b>11d</b> exhibiting optimal selectivity for HeLa and MCF-7 cells. This study provides important references for development of novel selenium-containing antitumor drugs.