Antiprotozoal Diterpenes from Perovskia abrotanoides

As part of a screening for new antiparasitic natural products from Iranian plants, n -hexane and ethyl acetate extracts from the aerial parts of Perovskia abrotanoides were found to exhibit strong inhibitory activity against Trypanosoma brucei rhodesiense and Leishmania donovani . The activity was tracked by high-performance liquid chromatography (HPLC)-based activity profiling. Preparative isolation by a combination of silica gel column chromatography and HPLC afforded 17 diterpenoids ( 1 – 17 ), including 14 abietane-, two icetexane-, and one isopimarane-type derivatives. Among these, (5 R ,10 S )-11-hydroxy-12-methoxy-20-norabieta-8,11,13-triene ( 2 ), 12-hydroxy-norabieta-1(10),8,11,13-tetraene-1,11-furan ( 6 ), and 12-methoxybarbatusol ( 9 ) were new compounds, the structure of which was established by comprehensive spectroscopic data analysis (one- and two-dimensional nuclear magnetic resonance, high-resolution electrospray ionization mass spectrometry, electronic circular dichroism). The antiprotozoal activity of the isolated compounds was evaluated against T. b. rhodesiense, Trypanosoma cruzi, L. donovani , and Plasmodium falciparum . Selectivity indexes (SI) were calculated in comparison to cytotoxicity on rat myoblast (L6) cells. Particularly active were 7 α -ethoxyrosmanol ( 4 ) with an IC 50 of 0.8 µM against T. b. rhodesiense (SI 14.9) and an IC 50 of 1.8 µM (SI 6.9) against L. donovani , ferruginol ( 8 ) with an IC 50 of 2.9 µM (SI 19.2) against P. falciparum , and miltiodiol ( 10 ) with an IC 50 of 0.5 µM (SI 10.5) against T. b. rhodesiense . None of the compounds exhibited selective toxicity against T. cruzi (SI ≤ 1.6).