(R)-(-)-Aloesaponol III 8-Methyl Ether from Eremurus persicus: A Novel Compound against Leishmaniosis.
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 againstLeishmaniainfections. 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 onEremurus persicusroot 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 fromEremurus persicusroot 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 inhibitsLeishmania infantumpromastigotes viability (IC5073 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 againstLeishmaniainfections.
Department of Drug Sciences, Medicinal Chemistry and Pharmaceutical Technology Section, University of Pavia, Viale Taramelli 12, 27100 Pavia, Italy. daniela.rossi@unipv.it.
Daniela
D
Rossi
Department of Drug Sciences, Medicinal Chemistry and Pharmaceutical Technology Section, University of Pavia, Viale Taramelli 12, 27100 Pavia, Italy. karzchem@yahoo.com.|Department of Science-Chemistry, University of Garmian, Kalar 46021, Kurdistan Region, Iraq. karzchem@yahoo.com.
Karzan Mahmood
KM
Ahmed
Department of Drug Sciences, Medicinal Chemistry and Pharmaceutical Technology Section, University of Pavia, Viale Taramelli 12, 27100 Pavia, Italy. raffaella.gaggeri@irst.emr.it.|Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) Srl-IRCCS Via Piero Maroncelli, 40, 47014 Meldola (FC), Italy. raffaella.gaggeri@irst.emr.it.
Raffaella
R
Gaggeri
Department of Drug Sciences, Medicinal Chemistry and Pharmaceutical Technology Section, University of Pavia, Viale Taramelli 12, 27100 Pavia, Italy. serena.dellavolpe01@universitadipavia.it.
Serena
S
Della Volpe
Department of Drug Sciences, Medicinal Chemistry and Pharmaceutical Technology Section, University of Pavia, Viale Taramelli 12, 27100 Pavia, Italy. lauretta.maggi@unipv.it.
Lauretta
L
Maggi
Dipartimento di Medicina Molecolare e Traslazionale, Università di Brescia, Viale Europa 11, 25123 Brescia, Italy. giuseppe.mazzeo@unibs.it.
Giuseppe
G
Mazzeo
Dipartimento di Medicina Molecolare e Traslazionale, Università di Brescia, Viale Europa 11, 25123 Brescia, Italy. giovanna.longhi@unibs.it.
Giovanna
G
Longhi
Dipartimento di Medicina Molecolare e Traslazionale, Università di Brescia, Viale Europa 11, 25123 Brescia, Italy. smrmachado@gmail.com.
Sergio
S
Abbate
Centro Grandi Strumenti, University of Pavia, Via Bassi 21, 27100 Pavia, Italy. federica.corana@unipv.it.
Federica
F
Corana
Department of Earth and Environmental Sciences, University of Pavia, Via S. Epifanio 14, 27100 Pavia, Italy. emanuela.martino@unipv.it.
Emanuela
E
Martino
CESPU, Instituto de Investigação e Formação Avançada em Ciências e Tecnologias da Saúde, 4585-116 Gandra PRD, Portugal. smrmachado@gmail.com.|CIBIO-UP, Centro de Investigação em Biodiversidade e Recursos Genéticos, Universidade do Porto, InBIO, 4485-661 Vairão, Portugal. smrmachado@gmail.com.
Marisa
M
Machado
Faculty of Pharmacy, University of Coimbra, Pólo das Ciências da Saúde, Azinhaga de Santa Comba, 3000-548 Coimbra, Portugal. raquel.varandas@ci.uc.pt.|CNC-Center for Neurosciences and Cell Biology, University of Coimbra, Rua Larga Faculty of Medicine, Pólo I, 3004-504 Coimbra, Portugal. raquel.varandas@ci.uc.pt.
Raquel
R
Varandas
Faculty of Pharmacy, University of Coimbra, Pólo das Ciências da Saúde, Azinhaga de Santa Comba, 3000-548 Coimbra, Portugal. mcsousa@ci.uc.pt.|CNC-Center for Neurosciences and Cell Biology, University of Coimbra, Rua Larga Faculty of Medicine, Pólo I, 3004-504 Coimbra, Portugal. mcsousa@ci.uc.pt.
Maria do Céu
MD
Sousa
Department of Drug Sciences, Medicinal Chemistry and Pharmaceutical Technology Section, University of Pavia, Viale Taramelli 12, 27100 Pavia, Italy. simona.collina@unipv.it.
Simona
S
Collina
D000818:Animals; D000880:Anthraquinones / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology / Q000627:therapeutic use*; D002452:Cell Count; D002453:Cell Cycle / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D002942:Circular Dichroism; D005434:Flow Cytometry; D018314:Leishmania infantum / Q000187:drug effects / Q000254:growth & development; D007896:Leishmaniasis / Q000188:drug therapy* / Q000469:parasitology; D008018:Life Cycle Stages / Q000187:drug effects; D008264:Macrophages / Q000166:cytology / Q000187:drug effects; D008738:Methyl Ethers / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology / Q000627:therapeutic use*; D051379:Mice; D000067996:RAW 264.7 Cells; D021241:Spectrometry, Mass, Electrospray Ionization; D000070380:Asphodelaceae
C000619276:(R)-aloesaponol III- 8 methyl ether; D000880:Anthraquinones; D008738:Methyl Ethers
(R)-aloesaponol III-8 methyl ether; Eremurus persicus; drug identification; leishmaniosis; plant extract