Synthesis and antiproliferative activity of silybin conjugates with salinomycin and monensin

Authors:

• Michał Antoszczak,
• Greta Klejborowska,
• Monika Kruszyk,
• Ewa Maj,
• Joanna Wietrzyk,
• Adam Włodzimierz Huczyński

Abstract

Aiming at development of multitarget drugs for the anticancer treatment, new silybin (SIL) conjugates with salinomycin (SAL) and monensin (MON) were synthesized, in mild esterification conditions, and their antiproliferative activity was studied. The conjugates obtained exhibit anticancer activity against HepG2, LoVo and LoVo/DX cancer cell lines. Moreover, MON-SIL conjugate exhibits higher anticancer potential and better selectivity than the corresponding SAL-SIL conjugate. The conjugates of hepatoprotective natural compound silybin (SIL) and two natural polyether ionophores monensin (MON) and salinomycin (SAL) displayed interesting antiproliferative activity in various human cancer cells, including MDR cells at low micromolar concentrations. The anticancer activity is connected with high selectivity indexes (SI) and low toxicity against normal cells.