Chemical and cytotoxic activity of three main sesquiterpenoids from Warburgia ugandensis

• Three sesquiterpenoids are efficiently isolated from Warburgia ugandensis stem bark in one process under mild conditions. • Warburgia ugandensis phytochemical profile is extended by 9-deoxymuzigadial. • The isolated sesquiterpenoids are cytotoxic against several cancer cell lines with IC 50 values between 0.44 µM and 22.40 µM. • The compounds are selectively effective against monocytic cells and solid cancer cells. • A mode-of-action model explaining the susceptibility of monocytic and solid cancer cells is highlighted. Plant materials of Warburgia ugandensis have long been used in traditional African medicine due to their broad spectrum of biological activity. Here, we describe an efficient and mild isolation of three major compounds polygodial 1a , warburganal 2a , and muzigadial 2b using Soxhlet extraction and combined preparative separation methods. Furthermore, 9-deoxymuzigadial was reported for the first time from this species. Since in silico analysis predicted drug-likeness, the compounds were tested against leukemia and solid cancer cell lines as well as human primary cells in vitro . The most susceptible cells were THP-1 indicating a selective effect against monocytes pointing towards a potential treatment of monocytic leukemia. The most robust cells were primary gingival fibroblasts offering selectivity also to solid cancers. The results in this study shed new light on long-known chemical compounds from traditional medicine and pave the way for in vivo studies to advance the substances to the next level towards the use as anti-cancer drugs.