Maria Helena Vendruscolo
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Gustavo Machado das Neves
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Luciano Porto Kagami
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Luiz Carlos Rodrigues Junior
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Maria Luísa Nunes Diehl
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...
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.
