Novel podophyllotoxin derivatives as Anticancer Agents: Design, Synthesis, and Biological Screening

The systemic treatment of advanced cancer, where local surgery is ineffective, still offers numerous difficulties due to therapy resistance, side effects and relapse. Thus, novel therapeutics are ongoing. The scaffolds for novel drugs often derive from naturally occurring substances. One of such example is podophyllotoxin – a plant derived substance. Podophyllotoxin itself is indicated in local anticancer treatment and due to its’ substantial toxicity is not recommend for systemic therapy. However, its analogues like etoposide is an element of systemic anticancer therapy administered in many malignancies. Limiting for etoposide is bone marrow depression and secondary leukemia induced in susceptible individuals. Thus, less toxic and more effective substances are needed for cancer therapy. Due to complexity of podophyllotoxin molecule it’s scaffold is nowadays intensively studied as a source for novel therapeutic substances. Within this project our team aimed to modify the molecule of podophyllotoxin to obtain novel derivatives that were screened for anticancer potential. Furthermore, one of new compound was conjugate of podophyllotoxin and benzothiazole. Benzothiazole is widely used in research because of antitumor, antibacterial, anticonvulsant, anti-inflammatory and other activities of its derivatives. The obtained derivates turned out to be less toxic for normal fibroblasts in comparison to parental podophyllotoxin.