Cytotoxic activity of compounds isolated from Dismerotemma aspilioides

GARCÍA MANZANO MARÍA FLORENCIA; JORAY MARIANA BELÉN; PALACIOS, SARA MARÍA; LAIOLO JERÓNIMO; CARPINELLA MARÍA CECILIA

Simposio; COST ACTION CM1407; 2017

Cancer is one of themajor threat to human health. The currently available cancer chemotherapy regimes may result in several critical problems,including lack of effectiveness, serious adverse effects and thedevelopment of multidrug resistance (MDR). Thus, more effective cancer therapies that result from the discovery of new drugs are of high priority.Plants have played a critical role in anticancer drug discovery. Plant or derived agents, including a variety of terpenoids,alkaloids, the epipodophyllotoxin lignanes, thetaxanes and the camptothecins, have been among the most widely used cancerchemotherapeutics available. The interest in the chemical diversity of the plant-derivedmetabolites is increasing with the aim of finding new hits or lead compounds for future chemotherapeutic drugs. In the search of theseentities, ninety three native and naturalized plants collected from central region of Argentina were screened fortheir anti-proliferative effect over the chronic myelogenous leukemia (CML) cell line K562.  Dimerostemmaaspilioides was selected as the plantwith the highest potential for processing in search of novel cytotoxicity principles.Theextraction and separation of Dimerostemma aspilioides were carriedout by bioguided isolation. The ethanol extractwas initially subjected to vacuum liquid chromatography on silica gel elutedwith a step gradient of hexane/ethyl acetate/methanol to yield 15 fractions,which where combined in 6 groups according to their thin layer chromatography(TLC) profile (F1 to F6). Of these, F4 and F5 demonstrated cytotoxic activityat concentrations < 2 µg/mL and were therefore submitted to additionalcolumn to yield 10 groups. Ofthese, F4,54-F4,55-F4,56 and F4,57 demonstrated cytotoxicity. From fractionF4,55, compound 1 was obtained by spontaneouscrystallization. Fraction F4,56 was further processedby flash chromatography, eluted with astep gradient of hexane/ethyl acetate/methanol. The fractions obtained werecombined in 8 groups (FI1 to FI8). Compound 2 wasobtained fom FI6 by extraction withacetonitrile/water/diethyl ether (25:25:50).       Onactivity assays, the cytotoxic effect was determined by MTT assay on K562.      The results obtained positionedthese structures as possible anticancer agents.