(R)-(-)-Aloesaponol III 8-Methyl Ether from Eremurus persicus: A Novel Compound against Leishmaniosis.

Daniela Rossi,Raquel Varandas,Emanuela Martino,Simona Collina,Giuseppe Mazzeo,Federica Corana,Serena Della Volpe,Marisa Machado,Sergio Abbate,Raffaella Gaggeri,Giovanna Longhi,Maria Sousa,Karzan Ahmed,Lauretta Maggi

doi:10.3390/molecules22040519

Abstract

Leishmaniosis is a neglected tropical disease which affects several millions of people worldwide. The current drug therapies are expensive and often lack efficacy, mainly due to the development of parasite resistance. Hence, there is an urgent need for new drugs effective against Leishmania infections. 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 the present study, we focused on Eremurus persicus root extract in order to evaluate its potential in the treatment of leishmaniosis. As a result of our study, aloesaponol III 8-methyl ether (ASME) was isolated for the first time from Eremurus persicus root extract, its chemical structure elucidated by means of IR and NMR experiments and the (R) configuration assigned by optical activity measurements: chiroptical aspects were investigated with vibrational circular dichroism (VCD) and electronic circular dichroism (ECD) spectroscopies and DFT (density functional theory) quantum mechanical calculations. Concerning biological investigations, our results clearly proved that (R)-ASME inhibits 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.

Highlights

Leishmaniosis, a neglected tropical disease (NTD), continues to be a major health problem, affecting 12 million people worldwide [1]
Given the long timeframes and generally low and hardly reproducible yields (3.9%–7.6%) of maceration, on the basis of our previous experience, we studied the applicability of microwave-assisted solvent extraction (MASE) to the extraction of E
We found that a rather short extraction time (20 min) afforded the ethanolic extract (EE) in higher yields (21.2%) compared to dynamic maceration

Summary

Introduction

Leishmaniosis, a neglected tropical disease (NTD), continues to be a major health problem, affecting 12 million people worldwide [1] This disease is caused by the Leishmania species, and is generally classified into three different clinical forms: visceral leishmaniosis (VL), cutaneous leishmaniosis (CL) and mucocutaneous leishmaniosis (MCL). VL can be fatal if left untreated, CL is localized and frequently self-heals within 3–18 months, while MCL leaves disfiguring scars New drugs, such as paromycin, miltefosine and liposomal amphotericin B, are available as antileishmanial therapy in several countries, currently pentavalent antimonials and amphotericin B are the most used drugs for such purpose. Still, they induce toxic effects, produce development of parasite resistance and, no less important, they are expensive [2]. Several plants and plant-derived natural products have been investigated so far as antileishmanial drug candidates [3,4]

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Conclusion