Antiprotozoal Sesquiterpene Lactones and Other Constituents from Tarchonanthus camphoratus and Schkuhria pinnata Njogu M. Kimani, † Josphat C. Matasyoh, ‡ Marcel Kaiser, §,# Reto Brun, §,# and Thomas J. Schmidt* ,† † Institute of Pharmaceutical Biology and Phytochemistry (IPBP), University of Muenster, PharmaCampus Corrensstrasse 48, Muenster D-48149, Germany ‡ Department of Chemistry, Egerton University, P.O. Box 536, Egerton 20115, Kenya § Swiss Tropical and Public Health Institute (Swiss TPH), Socinstrasse 57, Basel CH-4051, Switzerland # University of Basel, Petersplatz 1, Basel CH-4003, Switzerland *S Supporting Information ABSTRACT: In continuation of a search for new antiprotozoal agents from plants of the family Asteraceae, Tarchonanthus camphoratus and Schkuhria pinnata have been investigated. By following the promising in vitro activity of the dichloromethane extracts from their aerial parts, bioassay-guided chromatographic isolation yielded two known sesquiterpene lactones (1 and 2) from T. camphoratus and 20 known compounds of this type from S. pinnata. From the latter, a new eudesmanolide, (1R*,5S*,6R*,7R*,8R*,10R*)-1-hydroxy-8-[5″-hydroxy-4′-(2″-hydroxyisovaleroyloxy)- tigloyloxy]-3-oxoeudesma-11(13)-en-6,12-olide (3), and two new germacranolides, 3β- (2″-hydroxyisovaleroyloxy)-8β-(3-furoyloxy)costunolide (14) and 1(10)-epoxy-3β-hydroxy-8β-[5′ -hydroxy-4′ -(2″- hydroxyisovaleroyloxy)tigloyloxy]costunolide (16), were obtained. Additionally, the flavonoid pectolinarigenin (24) and 3- hydroxy-4,5-dimethoxybenzenepropanol (25) were also isolated from S. pinnata. The compounds were characterized by analysis of 1D and 2D NMR spectroscopic and HR/MS data. In vitro antitrypanosomal activity and cytotoxicity against mammalian cells (L6 cell line) were evaluated for all the compounds. Santhemoidin A (13) and 3β-(2″-hydroxyisovaleroyloxy)-8β-(3- furoyloxy)costunolide (14) were the most active compounds found in this study, with IC 50 values of 0.10 and 0.13 μM against Trypanosoma brucei rhodesiense trypomastigotes and selectivity indices of 20.5 and 29.7, respectively. I n the course of a continuing search for secondary metabolites from plants of the family Asteraceae with activity against protozoan parasites, a variety of natural products have been reported with interesting activity against Plasmodium falciparum and against species of the trypanosomatid genera Leishmania and Trypanosoma. 1-9 Several sesquiterpene lac- tones, characteristic constituents of this family of plants, have been shown to have interesting activity particularly against Trypanosoma brucei, the causative agent of human African trypanosomiasis. 1-4,10 Moreover, antiprotozoal flavonoids, alkamides, and chromene derivatives have been reported as well. 5-7 In the present study, the crude extracts of the Tarchonanthus camphoratus L. (Asteraceae, subfamily Carduoi- deae, tribe Tarchonantheae) and Schkuhria pinnata Lam. (Asteraceae, subfamily Asteroideae, tribe Heliantheae) leaves and aerial parts, respectively, were screened for antiprotozoal activity. The dichloromethane extracts displayed significant activity against T. brucei rhodesiense (Tbr) with IC 50 values of 0.61 and 0.64 μg/mL for T. camphoratus and S. pinnata, respectively. Furthermore, T. camphoratus was found to display considerable activity against L. donovani (Ldon), the etiological agent of visceral leishmaniasis, with an IC 50 value of 0.49 μg/ mL. Tarchonanthus camphoratus L. (Asteraceae) is an evergreen highly branched narrow-crowned shrub that grows up to 9 m high. It is native to Angola, Ethiopia, Kenya, Lesotho, Namibia, Somalia, South Africa, Tanzania, Uganda, and Zimbabwe, occurring in the savanna biome and woody grasslands. 11 The plant is used in folk medicine to treat bronchitis and chest ailments, tired legs and sore feet, stomach ailments, asthma, overanxiety, and heartburn. 11,12 The essential oil and solvent extracts have been reported to show antimicrobial activity. 13,14 An aqueous extract has been shown to have analgesic and antipyretic activity. 15 The sesquiterpene lactones costunolide, isocostic acid, 3β-hydroxy-1,2-dehydrocostic acid, and parthe- nolide have been reported from this plant as well as several sesquiterpene acid derivatives. 16 Schkuhria pinnata Lam. (Asteraceae) is an annual herb that grows as a weed to about 70 cm tall. It has numerous hairy erect stems with yellow flowers. It is native to South America but has been introduced into other countries. 17 It is reported to have been used to treat many ailments such as diabetes, malaria, diseases of the ear, nose, and throat, colds and influenza, wounds, kidney, liver, and renal problems, allergies, yeast infections, prostate inflammation, problems of the digestive tract, and rheumatism. 17-21 Previous studies have reported sesquiterpene lactones of the germacranolide type and flavonoids as its chemical constituents. 17,22 Received: August 31, 2017 Article pubs.acs.org/jnp Cite This: J. Nat. Prod. XXXX, XXX, XXX-XXX © XXXX American Chemical Society and American Society of Pharmacognosy A DOI: 10.1021/acs.jnatprod.7b00747 J. Nat. Prod. XXXX, XXX, XXX-XXX