Synthesis, cytotoxicity and antiplasmodial activity of novel ent-kaurane derivatives

This paper reports on the syntheses and spectrometric characterisation of eleven novel ent-kaurane diterpenoids, including a complete set of 1H, 13C NMR and crystallographic data for two novel ent-kaurane diepoxides. Moreover, the antineoplastic cytotoxicity for kaurenoic acid and the majority of ent-kaurane derivatives were assessed in vitro against a panel of fourteen cancer cell lines, of which allylic alcohols were shown to be the most active compounds. The good in vitro antimalarial activity and the higher selectivity index values observed for some ent-kaurane epoxides against the chloroquine-resistant W2 clone of Plasmodium falciparum indicate that this class of natural products may provide new hits for the development of antimalarial drugs.

Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slideHighlights► Synthesis of novel ent-kaurane diterpenoids. ► most of them disclosed low citotoxicity against fourteen cancer cell lines. ► epoxidized derivatives displayed good antiplasmodial activity with high selectivity. ► promising hits for the development of antimalarial drugs.