Proceedings of the Merck & Elsevier Young Chemists Symposium (MEYCS 2018)

Triple-negative breast cancer (TNBC) represents a clinical challenge with no approved targeted therapies [1]. Recently, correlations have emerged between the expression of G protein-coupled receptor 55 (GPR55) and both TNBC development and invasion, making it a promising key for the development of targeted therapies [2]. The 1,4-naphthoquinone framework exhibits a wide range of biological activities, including anticancer one [3]. A new series of 1,4-naphthoquinones, bearing various cyclic and aliphatic amines on C2, was designed and synthesized to identify antiproliferative agents for TNBC (Figure 1). Among naphthoquinones, compound 2a and 3a selectively inhibited the proliferation of MDA-MB-231 cells (EC50=1.6 μM and 2.7 μM, respectively), compared to normal human breast cells MCF10A. Furthermore, they did not affect the viability of peripheral blood mononuclear cells, suggesting their potential safer use for cancer treatment. Molecular docking studies were also carried out to support the in vitro results and suggested that compound 3a could exert its antiproliferative activity acting as a GPR55 antagonist.