Screening of 14 alkaloids isolated from Haplophyllum A. Juss. for their cytotoxic properties

Further to a systematic chemotaxonomic study of Uzbek Haplophyllum A. Juss. plants selected on ethnopharmacological data, 14 alkaloids were screened for their cytotoxic properties. As a first selection for interesting compounds, each alkaloid was tested against two human cancer cell lines (HeLa and HCT-116), using WST-1 reagent. Of the 14 alkaloids, 5 were cytotoxic when tested against the HeLa line with an IC50 < 100 mu M. These five compounds consisted of three furoquinolines: skimmianine; haplopine and gamma-fagarine and two pyranoquinolones: flindersine and haplamine. Only haplamine was active against the HCT-116 line. The cytotoxic properties of these five alkaloids were further investigated against five additional human cancer cell lines. Their structure-activity relationships will be discussed. Of these five pre-selected alkaloids, only haplamine showed significant cytotoxic activity against all the tested cell lines. This is the first report of the cytotoxic activity of haplamine. Finally, this pyranoquinolone alkaloid was tested here against 14 different cancer cell lines and against normal skin fibroblasts. (c) 2005 Elsevier Ireland Ltd. All rights reserved.