Dillapiole as antileishmanial agent: Discovery, cytotoxic activity and preliminary SAR studies of dillapiole analogues

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dc.contributor.authorParise-Filho R.
dc.contributor.authorPasqualoto K.F.M.
dc.contributor.authorMagri F.M.M.
dc.contributor.authorFerreira A.K.
dc.contributor.authorDa Silva B.A.V.G.
dc.contributor.authorDamiao M.C.F.C.B.
dc.contributor.authorTavares M.T.
dc.contributor.authorAzevedo R.A.
dc.contributor.authorAuada A.V.V.
dc.contributor.authorPolli M.C.
dc.contributor.authorBrandt C.A.
dc.date.accessioned2024-03-13T01:06:54Z
dc.date.available2024-03-13T01:06:54Z
dc.date.issued2012
dc.description.abstractIn this paper, the isolation of dillapiole (1) from Piper aduncum was reported as well as the semi-synthesis of two phenylpropanoid derivatives [di-hydrodillapiole (2), isodillapiole (3)], via reduction and isomerization reactions. Also, the compounds' molecular properties (structural, electronic, hydrophobic, and steric) were calculated and investigated to establish some preliminary structure-activity relationships (SAR). Compounds were evaluated for in vitro antileishmanial activity and cytotoxic effects on fibroblast cells. Compound 1 presented inhibitory activity against Leishmania amazonensis (IC 50 = 69.3 μM) and Leishmania brasiliensis (IC50 = 59.4 μM) and induced cytotoxic effects on fibroblast cells mainly in high concentrations. Compounds 2 (IC50 = 99.9 μM for L. amazonensis and IC50 = 90.5 μM for L. braziliensis) and 3 (IC50 = 122.9 μM for L. amazonensis and IC50 = 109.8 μM for L. brasiliensis) were less active than dillapiole (1). Regarding the molecular properties, the conformational arrangement of the side chain, electronic features, and the hydrophilic/hydrophobic balance seem to be relevant for explaining the antileishmanial activity of dillapiole and its analogues. Dillapiole (1) presented relevant effects against Leishmania amazonensis and L. brasiliensis. Additionally, compound 1 reduced fibroblast cell viability, indicating that this compound might have antileishmanial effects on non-phagocytic cells in the latent phase of the disease. SAR studies showed that the conformational arrangement and electronic properties as well as the hydro/lipophilic balance seem to be crucial for antileishmanial activity. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
dc.description.firstpage934
dc.description.issuenumber12
dc.description.lastpage944
dc.description.volume345
dc.identifier.doi10.1002/ardp.201200212
dc.identifier.issn0365-6233
dc.identifier.urihttps://dspace.mackenzie.br/handle/10899/36742
dc.relation.ispartofArchiv der Pharmazie
dc.rightsAcesso Restrito
dc.subject.otherlanguageAntileishmanial activity
dc.subject.otherlanguageCytotoxic activity
dc.subject.otherlanguageDillapiole
dc.subject.otherlanguageMolecular modeling
dc.subject.otherlanguageSAR studies
dc.titleDillapiole as antileishmanial agent: Discovery, cytotoxic activity and preliminary SAR studies of dillapiole analogues
dc.typeArtigo
local.scopus.citations33
local.scopus.eid2-s2.0-84870209712
local.scopus.updated2024-05-01
local.scopus.urlhttps://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=84870209712&origin=inward
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