The Use of Naphthoquinones and Furano-naphthoquinones as Anti-invasive Agents.

Cancer is a leading cause of mortality in the world and metastasis is to blame. Invasion is the initial step of metastasis. Therapies targeting epithelial-mesenchymal transition (EMT), cancer stem cells (CSCs) and signal transducer and activator of transcription 3 (STAT3) signaling pathways can reduce stemness of cancer cells and thus inhibit cancer invasion. A large number of anti-cancer naphthoquinones (NQs) can target cancer invasion by acting on EMT, CSCs and STAT3 signaling. Furano-naphthoquinones (FNQs) belong to a class of NQ derivatives commonly characterized by a naphthoquinone fused with a furano ring. A study indicated that the corporation of the furano ring improved the anticancer potency as compared to the other classes of NQs. BBI608, a natural FNQ, which can be found in the woods or barks of several Tabebuia species, has entered phases I and II clinical trials. It has been regarded as a potential candidate for new-generation lead compound acting directly on CSCs to overcome the chemotherapy resistance. Apart from the natural plant sources, there are a number of synthetic FNQ derivatives that are effective in reducing stemness of cancer cells and thus are anti-invasive. In this review, the anti-invasion mechanisms of NQs and the more powerful FNQs, together with their natural origins, synthetic derivatives as well as their synthetic routes are discussed.