In:
Current Topics in Medicinal Chemistry, Bentham Science Publishers Ltd., Vol. 22, No. 19 ( 2022-07), p. 1626-1633
Abstract:
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. Objective: 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 chromato-graphic 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 vibra-tional 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 , respectively. Further-more, this compound was non-toxic in J774 macrophage cells (CC50 〉 458.71 ) with a selectivi-ty index 〉 100 (promastigotes) and 〉 32.2 (amastigotes). Additionally, (–)-cyclocolorenone was ob-served 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.
Type of Medium:
Online Resource
ISSN:
1568-0266
DOI:
10.2174/1568026622666220707095718
Language:
English
Publisher:
Bentham Science Publishers Ltd.
Publication Date:
2022
SSG:
15,3
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