History and mechanism of action of niclosamide
Niclosamide is listed on the WHO list of essential medications and chewable tablets have been approved for use as an anti-helminthic agent for cestode (tapeworm) infections for over 40 years (Andrews, Thyssen, & Lorke, 1982). Animal studies have shown that niclosamide, has no mutagenic, oncogenic or embryotoxic activity. In humans it is rapidly eliminated by the kidneys with no cumulative toxic effects (Andrews et al., 1982). Structurally, niclosamide belongs to a large group of lipophilic, weakly acidic molecules called salicylanilides, a derivative of salicylic acid (Pearson & Hewlett, 1985). Niclosamide inhibits oxidative phosphorylation and stimulates ATP activity in the mitochondria of cestodes, killing both the scolex and the proximal segments of the tapeworm (Al-Hadiya, 2005; Weinbach & Garbus, 1969). In humans, it has been shown to affect several signal transduction pathways such as Wnt/β-catenin, mechanistic target of rapamycin (mTOR) complex 1 (mTORC1), signal transducer and activator of transcription 3 (STAT-3), nuclear factor-kappa B (NF-κB), Notch and NS2B-NS3, all indicating its potential to treat conditions such as cancer (summarised in Table 1), chronic medical diseases, and bacterial and viral infections.