The effects of new naphtoquinone and benzopyran derivatives studied in multi-drug resistant cancer cells

Multi-drug resistance (MDR) is a significant obstacle to the efficient treatment of cancer. Overexpression of membrane transporters P-glycoprotein (P-gp) and Breast Cancer Resistance Protein (BCRP) is responsible for the classic mechanism of MDR –the extrusion of drugs from cancer cells. The search for anti-cancer agents able to overcome or evade MDR has become an imperative in the field of drug design and discovery. Structure modification of natural products may still deliver new hope for the discovery of new scaffolds able to preserve cytotoxic activity toward MDR cancer cells. As a part of a research program aimed at studying new natural product–inspired compounds we synthesized some representative scaffolds containing a benzopyrane or a naphtoquinone core. Benzopyrans are privileged medicinal pharmacophores which appear as important structural components in natural compounds and generated great attention because of their interesting biological activity. Quinones are another class of important natural products showing remarkable anti-cancer activity, mostly connected with their redox properties. Based on our previous work, a series of naphtoquinones and benzopyrans were designed and synthesized. The compounds were tested in in vitro models of MDR (pairs of sensitive and MDR human cancer cell lines with different origin: non-small cell lung carcinoma, colorectal carcinoma and glioblastoma). Importantly, the characterization of MDR cancer cells revealed that they possess overexpression of P-gp or both P-gp and BCRP. The most potent compound, belonging to the class of naphtoquinones, reached IC50 in nanomolar range of concentrations in all the cell lines.