Aim. The study aimed to identify new pharmacologically active compounds among derivatives of 2-imino-2H-chromene-3-carboxylic acids, specifically through the synthesis of 1-naphthylamides of these acids and evaluation of their effects on cancer cell proliferation.

Materials and methods. Organic synthesis was performed, and the structures of the synthesized compounds were confirmed using instrumental analytical techniques. Pharmacological screening was subsequently conducted.

Results. N-(1-naphthyl)cyanoacetamide was obtained by reacting 1-naphthylamine with ethyl cyanoacetate under heating. This intermediate was then converted into N-(1 naphthyl)amides of 2-imino-2H-chromene-3-carboxylic acids via Knoevenagel condensation with salicylic aldehydes. The reaction was carried out in 2-propanol with piperidine as a catalyst. The in vitro antiproliferative activity of the synthesized compounds was tested against cell lines of common human tumors: leukemia (6 lines), lung cancer (9), colon cancer (7), renal cancer (8), ovarian cancer (6), prostate cancer (2), breast cancer (8), CNS tumors (6), and melanoma (8). Activity was assessed by comparing the optical density of cell cultures stained with sulforhodamine B before and after exposure to the test compounds dissolved in dimethyl sulfoxide.

Conclusions. In vitro testing revealed that 7-hydroxy-2-imino-2H-chromene-3-[N-(1-naphthyl)]carboxamide (4d) exhibited the highest activity, significantly inhibiting the growth of most cultures (GI50 1.5–4.5 μM), with potency equal to or exceeding that of the reference drug. Furthermore, 6-methoxy-2-imino-2H-chromene-3-[N-(1-naphthyl)]carboxamide (4b) showed pronounced selectivity and efficacy against breast cancer cell lines MDA MB 435 (GI50 0.32 μM) and MDA N (GI50 0.46 μM), surpassing the reference drug severalfold. These findings experimentally confirm that the presence of a hydroxyl group at the 7th position of the 2H-chromene ring enhances activity, consistent with literature reports on the ability of related amides to inhibit tyrosine kinase enzymes.