Salinomycin and its derivatives - A new class of multiple-targeted "magic bullets"

The history of drug development clearly shows the scale of painstaking effort leading to a finished product a highly biologically active agent that would be at the same time no or little toxic to human organism. Moreover, the aim of modern drug discovery can move from "one-molecule one-target" concept to more promising "one-molecule multiple-targets" one, particularly in the context of effective fight against cancer and other complex diseases. Gratifyingly, natural compounds are excellent source of potential drug leads. One of such promising naturally-occurring drug candidates is a polyether ionophore salinomycin (SAL). This compound should be identified as multi-target agent for two reasons. Firstly, SAL combines a broad spectrum of bioactivity, including antibacterial, antifungal, antiviral, antiparasitic and anticancer activity, with high selectivity of action, proving its significant therapeutic potential. Secondly, the multimodal mechanism of action of SAL has been shown to be related to its interactions with multiple molecular targets and signalling pathways that are synergistic for achieving a therapeutic anticancer effect. On the other hand, according to the Paul Ehrlich's "magic bullet" concept, invariably inspiring the scientists working on design of novel target-selective molecules, a very interesting direction of research is rational chemical modification of SAL. Importantly, many of SAL derivatives have been found to be more promising as chemotherapeutics than the native structure. This concise review article is focused both on the possible role of SAL and its selected analogues in future antimicrobial and/or cancer therapy, and on the potential use of SAL as a new class of multiple-targeted "magic bullet" because of its multimodal mechanism of action. (C) 2019 Elsevier Masson SAS. All rights reserved.