Nature aided drug discovery. Novel Compounds against Leishmaniasis from Eremurus persicus.

Current therapies against Leishmaniosis include a limited range of drugs with high toxicity and moderate efficacy. Some recent works have demonstrated the potential of natural products as a rich source of novel scaffold for development of new drugs and drug candidates in general, and for anti-leishmaniosis drugs, in particular. Looking for new compounds potentially effective in the treatment of leishmaniosis, we face a Nature Aided Drug Discovery approach, as a part of our ongoing study on the phytochemical characterization and biological investigation of plants used in the traditional medicine of western and central Asia. In this communication, we will share the results of our study Eremurus persicus Boiss. We prepared an E. persicus root extract and, following a bio-guided assay approach, we isolated (R)-aloesaponol III 8-methyl ether [(R)-ASME] which structure was elucidated by means of IR and NMR experiments and the configuration assigned by chiroptical measurements. Of note, (R)-ASME was isolated for the first time from E. persicus. Afterwards, we optimized the experimental conditions to extract (R)-ASME from plant exhaustively. Applying a microwaveassisted extraction (MAE) and using ethanol as solvent (R)-ASME was obtained in high yields (2.5 mg/g dried plant), using a low amount of solvent and low waste of time. From a biological point of view, we demonstrated that (R)-ASME is able to inhibit Leishmania infantum promastigotes viability (IC50 73 μg/mL), inducing morphological alterations and mitochondrial potential deregulation. Moreover, it is not toxic on macrophages at the concentration tested, thus representing a promising molecule against Leishmania infections. Considering the great potential of (R)-ASME, our ongoing efforts are addressed to obtain hydrosoluble derivatives. Moreover, a biotin-conjugated (R)-ASME derivative will be also prepared, to increase the cellular uptake, thus improving drug efficacy.