Phytochemical study of Seriphidium khorassanicum (syn. Artemisia khorassanica) aerial parts: sesquiterpene lactones with anti-protozoal activity

Two new eudesmane-type sesquiterpene lactones, 1 beta,3 alpha,8 alpha-trihydroxy-11 beta,13-dihydroeudesma-4(15)-en-12,6 alpha-olide (1) and 1 beta,4 alpha,8 alpha-trihydroxy-11 beta,13-dihydroeudesma-12,6 alpha-olide (2), and an unprecedented elemane-type sesquiterpene lactone, 1 beta,2 beta,8 alpha-trihydroxy-11 beta,13-dihydroelema-12,6 alpha-olide (3) along with a known eudesmanolide artapshin (4) were isolated from Seriphidium khorassanicum. Structures were elucidated by NMR, HR-ESI-MS, and ECD spectral data analysis. The anti-protozoal activity was evaluated against Leishmania major promastigotes and amastigote-infected macrophages. They showed dose- and time-dependent activity against L. major amastigotes with IC50 values in the range of 4.9 to 25.3 mu M being favourably far below their toxicity against normal murine macrophages with CC50 values ranging from 432.5 to 620.7 mu M after 48 h of treatment. Compound 3 exhibited the strongest activity and the highest selectivity index (SI) with IC50 of 4.9 +/- 0.6 mu M and SI of 88.2 comparable with the standard drug, meglumine antimoniate (Glucantime), with IC50 and SI values of 15.5 +/- 2.1 mu M and 40.0, respectively.

Automated summary

Two new eudesmane-type sesquiterpene lactones and an unprecedented elemane-type sesquiterpene lactone were isolated from Seriphidium khorassanicum. They showed dose- and time-dependent activity against Leishmania major amastigotes, with one compound exhibiting the strongest activity and highest selectivity index.