Abstract
Two new eudesmane-type sesquiterpene lactones, 1β,3α,8α-trihydroxy-11β,13-dihydroeudesma-4(15)-en-12,6α-olide (1) and 1β,4α,8α-trihydroxy-11β,13-dihydroeudesma-12,6α-olide (2), and an unprecedented elemane-type sesquiterpene lactone, 1β,2β,8α-trihydroxy-11β,13-dihydroelema-12,6α-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 μM being favourably far below their toxicity against normal murine macrophages with CC50 values ranging from 432.5 to 620.7 μM after 48 h of treatment. Compound 3 exhibited the strongest activity and the highest selectivity index (SI) with IC50 of 4.9 ± 0.6 μM and SI of 88.2 comparable with the standard drug, meglumine antimoniate (Glucantime), with IC50 and SI values of 15.5 ± 2.1 μM and 40.0, respectively.
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