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In vitro and in silico Activity of Iridoids Against Leishmania amazonensis

[ Vol. 16 , Issue. 2 ]

Author(s):

Maria Helena Vendruscolo, Gustavo Machado das Neves, Luciano Porto Kagami, Luiz Carlos Rodrigues Junior, Maria Luísa Nunes Diehl, Simone Cristina Baggio Gnoatto, Sérgio Augusto de Loreto Bordignon, Pedro Roosevelt Torres Romão, Vera Lucia Eifler-Lima and Gilsane Lino von Poser*   Pages 173 - 183 ( 11 )

Abstract:


Background: Leishmaniasis reaches millions of people around the world. The control of the disease is difficult due to the restricted access to the diagnosis and medication, and low adherence to the treatment. Thus, more efficient drugs are needed and natural products are good alternatives. Iridoids, natural products with reported leishmanicidal activity, can be exploited for the development of anti- Leishmania drugs. The aim of this study was to isolate and to investigate the in vitro activity of iridoids against Leishmania amazonensis and to compare the activity in silico of these compounds with those reported as active against this parasite.

Methods: Iridoids were isolated by chromatographic methods. The in vitro activity of asperuloside (1) and geniposide (2) from Escalonia bifida, galiridoside (3) from Angelonia integerrima and theveridoside (4) and ipolamiide (5) from Amphilophium crucigerum was investigated against promastigote forms of Leishmania amazonensis. Molecular modeling studies of 1-5 and iridoids cited as active against Leishmania spp. were performed.

Results: Compounds 1-5 (5-100 µM) did not inhibit the parasite survival. Physicochemical parameters predicted for 1-5 did not show differences compared to those described in literature. The SAR and the pharmacophoric model confirmed the importance of maintaining the cyclopentane[C]pyran ring of the iridoid, of oxygen-linked substituents at the C1 and C6 positions and of bulky substituents attached to the iridoid ring to present leishmanicidal activity.

Conclusion: The results obtained in this study indicate that iridoids are a promising group of secondary metabolites and should be further investigated in the search for new anti-Leishmania drugs.

Keywords:

Iridoids, Escalonia bifida, Angelonia integerrima, Amphilophium crucigerum, Leishmania, leishmanicidal activity, molecular modeling, pharmacophore.

Affiliation:

Post-graduate Program in Pharmaceutical Sciences, College of Pharmacy, Federal University of Rio Grande do Sul (UFRGS), Porto Alegre, Post-graduate Program in Pharmaceutical Sciences, College of Pharmacy, Federal University of Rio Grande do Sul (UFRGS), Porto Alegre, Post-graduate Program in Pharmaceutical Sciences, College of Pharmacy, Federal University of Rio Grande do Sul (UFRGS), Porto Alegre, Post-Graduate Program in Health Sciences, Department of Basic Health Sciences, College of Pharmacy, Federal University of Health Sciences of Porto Alegre (UFCSPA), Porto Alegre, Post-graduate Program in Pharmaceutical Sciences, College of Pharmacy, Federal University of Rio Grande do Sul (UFRGS), Porto Alegre, Post-graduate Program in Pharmaceutical Sciences, College of Pharmacy, Federal University of Rio Grande do Sul (UFRGS), Porto Alegre, Post-Graduate Program in Environmental Impact Assessment, College of Pharmacy, La Salle University Center (UNILASALLE), Canoas, Post-Graduate Program in Health Sciences, Department of Basic Health Sciences, College of Pharmacy, Federal University of Health Sciences of Porto Alegre (UFCSPA), Porto Alegre, Post-graduate Program in Pharmaceutical Sciences, College of Pharmacy, Federal University of Rio Grande do Sul (UFRGS), Porto Alegre, Post-graduate Program in Pharmaceutical Sciences, College of Pharmacy, Federal University of Rio Grande do Sul (UFRGS), Porto Alegre

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