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

Abstract

Two new eudesmane-type sesquiterpene lactones, 1beta,3alpha,8alpha-trihydroxy-11beta,13-dihydroeudesma-4(15)-en-12,6alpha-olide (1) and 1beta,4alpha,8alpha-trihydroxy-11beta,13-dihydroeudesma-12,6alpha-olide (2), and an unprecedented elemane-type sesquiterpene lactone, 1beta,2beta,8alpha-trihydroxy-11beta,13-dihydroelema-12,6alpha-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 IC(50) values in the range of 4.9 to 25.3 muM being favourably far below their toxicity against normal murine macrophages with CC(50) values ranging from 432.5 to 620.7 muM after 48 h of treatment. Compound 3 exhibited the strongest activity and the highest selectivity index (SI) with IC(50) of 4.9 +/- 0.6 muM and SI of 88.2 comparable with the standard drug, meglumine antimoniate (Glucantime), with IC(50) and SI values of 15.5 +/- 2.1 muM and 40.0, respectively.