Absolute Configuration and Antileishmanial Activity of (–)-Cyclocolorenone
Isolated from Duguetia lanceolata (Annonaceae)

Jackson      Monteiro; Luiz   Felipe D.   Passero; Jéssica   A.   Jesus; Márcia   D.   Laurenti; João   H. G.   Lago; Marisi   G.   Soares; Andrea   N. L.   Batista; João   M.   Batista; Patricia      Sartorelli

doi:10.2174/1568026622666220707095718

Abstract

Background: The fractionation of the n-hexane phase of the EtOH extract from the leaves of Duguetia lanceolata (Annonaceae) led to the identification of the sesquiterpene (–)-cyclocolorenone.

Objectives: Chemical characterization, including determination of the absolute stereochemistry, and in vitro evaluation of antileishmanial activity of the sesquiterpene (–)-cyclocolorenone, isolated from D. lanceolata, were carried out.

Methods: (–)-Cyclocolorenone was isolated from D. lanceolata leaves using different chromatographic steps and its structure was defined by analysis of NMR and ESI-HRMS data. Additionally, the absolute configuration of (–)-cyclocolorenone was ambiguously assigned by means of vibrational circular dichroism (VCD). Antileishmanial activity of (–)-cyclocolorenone was evaluated on promastigote and amastigote forms of Leishmania (Leishmania) amazonensis. The integrity of the cell membrane of L. (L.) amazonensis was analyzed using the SYTOX green probe.

Results: (–)-(1R,6S,7R,10R)-Cyclocolorenone displayed activity against promastigotes and amastigotes forms of L. (L.) amazonensis with IC₅₀ of 4.54 and 28.44 µM, respectively. Furthermore, this compound was non-toxic in J774 macrophage cells (CC₅₀ > 458.71 µM) with a selectivity index > 100 (promastigotes) and > 32.2 (amastigotes). Additionally, (–)-cyclocolorenone was observed to target the parasite cell membrane.

Conclusion: Obtained data suggested that (–)-cyclocolorenone, in which absolute configuration was determined, can be considered as a scaffold for the development of new drugs for the treatment of leishmaniasis.

Keywords: Duguetia lanceolata, (–)-Cyclocolorenone, VCD, Antileishmanial activity, Cell membrane, Macrophage cells.

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DOI https://dx.doi.org/10.2174/1568026622666220707095718	Print ISSN 1568-0266
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Absolute Configuration and Antileishmanial Activity of (–)-Cyclocolorenone Isolated from Duguetia lanceolata (Annonaceae)

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