Cyanobacterial natural products – important environmental toxins and leads for drug substance development

Cyanobacteria are famous for the production of toxins such as microcystins, saxitoxins, anatoxins, and cylindrospermopsins. However, “toxin” is a denouncing term for “compound with impressing biological activiy” – and as we know, the dose (but also the route of administration and other details) makes the poison. None of the drug substances on the market today is free of toxicity if misused. Thus, also cyanobacterial “toxins” might serve as lead compounds for drug development. In the first part of this talk, I will give an overview over cyanobacterial toxins, both discussing their environmental impact and their potential for drug development.

In the second part of the talk, I will focus on microcystins, potent inhibitors of protein phosphatases known as cyanotoxins causing severe liver damage. However, due to their pronounced cytotoxicity and intriguing pharmacokinetic properties, they could potentially be used as anti-cancer drugs. Using precursor-directed biosynthesis, we have developed easy-to-derivatize microcystins that can potentially be used as payloads in antibody-drug conjugates (ADCs) for targeted cancer therapy. First steps of the structure optimization and bioactivity characterization of microcystins as lead structures are presented.