Zimmermann, SFouché, GerdaDe Mieri, MYukiko, YToyonobu, UNthambeleni, RParkinson, CJVan der Westhuyzen, Christiaan WKaiser, MHamburger, MAdams, M2015-08-172015-08-172014-03Zimmermann, S.,Fouché, G., De Mieri, M., Yukiko, Y., Toyonobu, U., Nthambeleni, R., Parkinson, C.J., Van der Westhuyzen, C., Kaiser, M., Hamburger, M., and Adams, M.,2015. Structure-activity relationship study of sesquiterpene lactones and their semi-synthetic amino derivatives as potential antitrypanosomal products. Molecules Journal, Vol.19, pp. 1-161420-3049http://hdl.handle.net/10204/8020Copyright: 2014 MDPI AG, Basel, Switzerland.Sesquiterpene lactones (STLs) are natural products that have potent antitrypanosomal activity in vitro and, in the case of cynaropicrin, also reduce parasitemia in the murine model of trypanosomiasis. To explore their structure-antitrypanosomal activity relationships, a set of 34 natural and semi-synthetic STLs and amino-STLs was tested in vitro against T. b. rhodesiense (which causes East African sleeping sickness) and mammalian cancer cells (rat bone myoblast L6 cells). It was found that the α-methylene-γ- lactone moiety is necessary for both antitrypanosomal effects and cytotoxicity. Antitrypanosomal selectivity is facilitated by 2-(hydroxymethyl)acrylate or 3,4-dihydroxy-2-methylenebutylate side chains, and by the presence of cyclopentenone rings. Semi-synthetic STL amines with morpholino and dimethylamino groups showed improved in vitro activity over the native STLs. The dimethylamino derivative of cynaropicrin was prepared and tested orally in the T. b. rhodesiense acute mouse model, where it showed reduced toxicity over cynaropicrin, but also lost antitrypanosomal activity.enCynaropicrinSesquiterpene lactonesAntitrypanosomalCytotoxicityStructure-activity-relationshipDimethylamino analoguesT. b. rhodesiense acute mouse modelArticleZimmermann, S., Fouché, G., De Mieri, M., Yukiko, Y., Toyonobu, U., Nthambeleni, R., ... Adams, M. (2014). Structure-activity relationship study of sesquiterpene lactones and their semi-synthetic amino derivatives as potential antitrypanosomal products. http://hdl.handle.net/10204/8020Zimmermann, S, Gerda Fouché, M De Mieri, Y Yukiko, U Toyonobu, R Nthambeleni, CJ Parkinson, et al "Structure-activity relationship study of sesquiterpene lactones and their semi-synthetic amino derivatives as potential antitrypanosomal products." (2014) http://hdl.handle.net/10204/8020Zimmermann S, Fouché G, De Mieri M, Yukiko Y, Toyonobu U, Nthambeleni R, et al. Structure-activity relationship study of sesquiterpene lactones and their semi-synthetic amino derivatives as potential antitrypanosomal products. 2014; http://hdl.handle.net/10204/8020.TY - Article AU - Zimmermann, S AU - Fouché, Gerda AU - De Mieri, M AU - Yukiko, Y AU - Toyonobu, U AU - Nthambeleni, R AU - Parkinson, CJ AU - Van der Westhuyzen, Christiaan W AU - Kaiser, M AU - Hamburger, M AU - Adams, M AB - Sesquiterpene lactones (STLs) are natural products that have potent antitrypanosomal activity in vitro and, in the case of cynaropicrin, also reduce parasitemia in the murine model of trypanosomiasis. To explore their structure-antitrypanosomal activity relationships, a set of 34 natural and semi-synthetic STLs and amino-STLs was tested in vitro against T. b. rhodesiense (which causes East African sleeping sickness) and mammalian cancer cells (rat bone myoblast L6 cells). It was found that the α-methylene-γ- lactone moiety is necessary for both antitrypanosomal effects and cytotoxicity. Antitrypanosomal selectivity is facilitated by 2-(hydroxymethyl)acrylate or 3,4-dihydroxy-2-methylenebutylate side chains, and by the presence of cyclopentenone rings. Semi-synthetic STL amines with morpholino and dimethylamino groups showed improved in vitro activity over the native STLs. The dimethylamino derivative of cynaropicrin was prepared and tested orally in the T. b. rhodesiense acute mouse model, where it showed reduced toxicity over cynaropicrin, but also lost antitrypanosomal activity. DA - 2014-03 DB - ResearchSpace DP - CSIR KW - Cynaropicrin KW - Sesquiterpene lactones KW - Antitrypanosomal KW - Cytotoxicity KW - Structure-activity-relationship KW - Dimethylamino analogues KW - T. b. rhodesiense acute mouse model LK - https://researchspace.csir.co.za PY - 2014 SM - 1420-3049 T1 - Structure-activity relationship study of sesquiterpene lactones and their semi-synthetic amino derivatives as potential antitrypanosomal products TI - Structure-activity relationship study of sesquiterpene lactones and their semi-synthetic amino derivatives as potential antitrypanosomal products UR - http://hdl.handle.net/10204/8020 ER -