Preparation of Sesquiterpene Lactone Derivatives: Cytotoxic Activity and Selectivity of Action

Cancer is one of the most important causes of death worldwide. Solid tumors represent the great majority of cancers (>90%) and the chemotherapeutic agents used for their treatment are still characterized by variable efficacy and toxicity. Sesquiterpene lactones are a group of naturally occurring compounds that have displayed a diverse range of biological activities including cytotoxic activity. A series of oxygenated and oxy-nitrogenated derivatives ( ⁻ ) from the sesquiterpene lactones cumanin ( ), helenalin ( ), and hymenin ( ) were synthesized. The silylated derivatives of helenalin, compounds and , were found to be the most active against tumor cell lines, with GI values ranging from 0.15 to 0.59 μM. The ditriazolyl cumanin derivative ( ) proved to be more active and selective than cumanin in the tested breast, cervix, lung, and colon tumor cell lines. This compound was the least toxic against splenocytes (CC = 524.1 µM) and exhibited the greatest selectivity on tumor cell lines. This compound showed a GI of 2.3 µM and a SI of 227.9 on WiDr human colon tumor cell lines. Thus, compound can be considered for further studies and is a candidate for the development of new antitumor agents.