New antiprotozoal sesquiterpene derivatives from Dorema glabrum Fisch & CAMey

Seven undescribed sesquiterpene derivatives, Azerins A-G (3-6, 8, 14 and 15), three known sesquiterpene phenols, kopetdaghin A (1), kopetdaghin B (2) and latisectin (7), together with five known sesquiterpene cou-marins (9-13), were isolated from the roots of Dorema glabrum. The structures were elucidated by comprehensive 1D-and 2D-NMR spectral analysis as well as HR-ESI-MS. Compounds were assessed for their in vitro antiprotozoal activity against Trypanosoma brucei rhodesiense, T. cruzi, Leishmania donovani, and Plasmodium falciparum. Cytotoxic potentials of the compounds were also tested on L6 rat skeletal myoblasts. Azerin G (15) showed a potent preferential growth inhibitory activity against T. b. rhodesiense with IC50 value of 0.01 mu M and selectivity index of 329. Compounds 1, 4, 7 and 8 were also found as the most active compounds with selective growth inhibitory effects toward P. falciparum with selectivity indices ranging from 11.6 to 16.7 (IC50: 1.8-24.6 mu M).

Automated summary

Seven undescribed sesquiterpene derivatives, Azerins A-G (3-6, 8, 14 and 15), along with known sesquiterpene phenols (1, 2 and 7) and sesquiterpene coumarins (9-13), were isolated from the roots of Dorema glabrum. Their structures were determined using NMR and MS techniques. The compounds were evaluated for their antiprotozoal and cytotoxic activities, and Azerin G (15) exhibited potent growth inhibitory activity against T. b. rhodesiense, while compounds 1, 4, 7, and 8 showed selective inhibitory effects on P. falciparum.