Cytotoxic activity of compounds isolated from Dismerotemma aspilioides

GARCIA MANANO M.F.; JORAY M.B.; PALACIOS S. M.; LAIOLO J.; CARPINELLA M. C.

Taller; COST Action CM1407 Challenging organic synthesis inspired by nature-form natural products chemistry to drug discovery. Training School; 2017

Cancer is one of the major threat to human health. The currently available cancer chemotherapy regimes may result in several critical problems, including lack of effectiveness, serious adverse effects and the development 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, the taxanes and the camptothecins, have been among the most widely used cancer chemotherapeutics available. The interest in the chemical diversity of the plant-derived metabolites is increasing with the aim of finding new hits or lead compounds for future chemotherapeutic drugs. In the search of these entities, ninety three native and naturalized plants collected from central region of Argentina were screened for their anti-proliferative effect over the chronic myelogenous leukemia (CML) cell line K562. Dimerostemma aspilioides was selected as the plant with the highest potential for processing in search of novel cytotoxicity principles.The extraction and separation of Dimerostemma aspilioides were carried out by bioguided isolation. The ethanol extract was initially subjected to vacuum liquid chromatography on silica gel eluted with 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 activity at concentrations < 2 µg/mL and were therefore submitted to additional column to yield 10 groups. Of these, F4,54-F4,55-F4,56 and F4,57 demonstrated cytotoxicity. From fraction F4,55, compound 1 was obtained by spontaneous crystallization. Fraction F4,56 was further processed by flash chromatography, eluted with a step gradient of hexane/ethyl acetate/methanol. The fractions obtained were combined in 8 groups (FI1 to FI8). Compound 2 was obtained fom FI6 by extraction with acetonitrile/water/diethyl ether (25:25:50). On activity assays, the cytotoxic effect was determined by MTT assay on K562. The results obtained positioned these structures as possible anticancer agents.