Submitted to: Miscellaneous Publishing Information Bulletin
Publication Type: Peer reviewed journal
Publication Acceptance Date: 5/18/2006
Publication Date: 8/1/2006
Citation: Fokialakis, N., Kalpoutzakis, E., Tekwani, B.L., Skaltsounis, A.L., Duke, S.O. 2006. Antileishmanial Activity of Natural Diterpenes from Cistus sp. and Semisynthetic Derivatives Thereof. Biological and Pharmaceutical Bulletin. 29(8):1775-1778. Interpretive Summary: Leishmaniasis is a public health problem in many parts of the world. Eleven cis-clerodane diterpenes, seven labdane type diterpenes and one triterpene isolated from two species of the plant genus Cistus were evaluated through in vitro bioassays against Leishmania donovani, the causative agent for visceral leishmaniasis. In addition, 28 synthetic compounds, based on these natural compounds, were generated and evaluated. Three compounds (two natural and one synthetic) were found to have greater activity than the pharmaceutical pentamidine in killing 90% of the parasites.
Technical Abstract: Eleven cis-clerodane diterpenes, seven labdane type diterpenes and one triterpene isolated from Cistus monspeliensis and the resin "Ladano" of Cistus creticus subsp. creticus were evaluated against Leishmania donovani promastigotes, the causative agent for visceral leishmaniasis. In addition, eleven hemisynthetic manoyl oxide, seventeen labdane type derivatives and a triterpene were also evaluated for their antileishmanial activity. 18-Acetoxy-3-ene-cis-clerodan-15-ol, 15,18-diacetoxy-3-ene-cis-clerodane and 13-(E)-labda-13-ene-8a-ol-15-yl-2-chloroethylcarbamate exhibited the most potent and selective leishmanicidal activity with IC50 values of 3.3 ug/ml, 3.4 ug/ml and 3.5 ug/ml, respectively.