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.
摘要：
两种新的Eudesmane型倍半萜内酯，1β,3α,8α-三羟基-11β，13-二氢Eudesma-4（15）-en-12,6α-内酯（1）和1β，4α,8α-三羟基-11β，13-二氢Eudesma-12,6α-内酯(2)，和前所未有的elemane型倍半萜内酯，1β,2β,8α-三羟基-11β，从Horassanicum分离出13-二氢elema-12,6α-内酯（3）和已知的Eudesmanolideartapshin（4）。结构由NMR阐明,HR-ESI-MS,和ECD光谱数据分析。针对主要的利什曼原虫和amastigote感染的巨噬细胞评估了抗原生动物活性。他们对主要的amastigotes具有剂量和时间依赖性活性，IC50值在4.9至25.3μM范围内，远远低于其对正常鼠巨噬细胞的毒性，CC50值在48小时后在432.5至620.7μM范围内治疗。化合物3表现出最强的活性和最高的选择性指数（SI），IC50为4.9±0.6μM，SI为88.2，与标准药物相当。锑酸葡甲胺（葡聚糖时间），IC50和SI值分别为15.5±2.1μM和40.0。
