From nature a new compound against Leishmania infantum

Despite the urgent need for efficient medical treatments against Leishmania, today a limited number of drug candidates are available. With the aim to perform a nature-aided drug discovery, we focused on secondary metabolites by Eremurus persicus roots. As a result of our investigation, we isolated (R)- Aloesaponol III 8-methyl ether, (R)-ASME, showing a remarkable antiprotozoal effect against L. infantum with an IC50 of 73 μg/mL and not significant toxicity in a macrophage cell line. The potential of this compound have led us to further investigate its properties. First of all, we optimized the experimental conditions to extract (R)-ASME from plant exhaustively. Applying a microwave-assisted extraction (MAE) and using ethanol as solvent, (R)-ASME was obtained in high yields (2.5 mg/g dried plant), using low amount of solvent and low waste of time. In the meanwhile, we have tried to improve (R)-ASME solubility. To improve this critical property of the considered hit, different molecular modification strategies have been tried. The investigated approaches consisted in the conjugation of (R)-ASME with either amino acid, since it is considered a useful method for increase compound water solubility, or with an hydrophilic moiety, such as a diethilenglycolic chain. Both of these approaches have brought us to obtain unstable derivates. Further trials will be done considering other hydrophilic groups. Moreover, to improve cellular uptake, and following a drug targeting approach ongoing efforts will be addressed to prepare a biotin-conjugated (R)-ASME derivative. Results will be presented in due course.