parthenin and Neoplasms

Analogues of parthenin were synthesized by substitutions at different reaction centres to establish a structure-activity relationship (SAR). Some of the molecules have displayed significant cytotoxicity in human cervical carcinoma (HeLa) and human myeloid leukemia (HL-60) cells. A few of the compounds also induced apoptosis in HL-60 cells measured in terms of sub-Go/G1 DNA fraction. Also one of the lead molecules has been shown to be the inhibitor of both telomerase and topoisomerase-II.

Topics: Antineoplastic Agents; Apoptosis; Chemistry, Pharmaceutical; Drug Design; HeLa Cells; HL-60 Cells; Humans; Inhibitory Concentration 50; Models, Chemical; Neoplasms; Plasmids; Sesquiterpenes; Structure-Activity Relationship; Telomerase; Topoisomerase II Inhibitors

Some sesquiterpene lactones (SLs) are the active compounds of a great number of traditionally medicinal plants from the Asteraceae family and possess considerable cytotoxic activity. Several studies in vitro have shown the inhibitory activity against cells derived from human carcinoma of the nasopharynx (KB). In this study, we investigated a set of 37 different sesquiterpene lactones, represented by 4 skeletons (14 germacranolides, 6 elemanolides, 9 guaianolides and nor-derivatives, and 8 pseudoguaianolides), in what it says respect of their cytotoxic properties. The experimental results were submitted to a QSAR study. A single model for the entire data set was described using 3D molecular descriptors and genetic algorithms establishing structure-activity relationships among the compounds. Important properties for the inhibition potency are discussed for the whole data set and for subsets of the different structural skeletons.

Topics: Algorithms; Antineoplastic Agents, Phytogenic; Artificial Intelligence; Asteraceae; Cell Line, Tumor; Chemical Phenomena; Chemistry, Physical; Humans; Models, Statistical; Neoplasms; Quantitative Structure-Activity Relationship; Regression Analysis; Sesquiterpenes; Structure-Activity Relationship