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

Author:

Batista João M.1,Sartorelli Patricia2ORCID,Monteiro Jackson2,Passero Luiz Felipe D.34ORCID,Jesus Jéssica A.5ORCID,Laurenti Márcia D.5ORCID,Lago João H. G.6,Soares Marisi G.7,Batista Andrea N. L.8

Affiliation:

1. Instituto de Ciência e Tecnologia, Universidade Federal de São Paulo, São José dos Campos, Brazil

2. Instituto de Ciências Ambientais, Químicas e Farmacêuticas, Universidade Federal de São Paulo, Diadema, Brazil

3. Instituto de Biociências, Universidade Estadual Paulista, São Vicente, Brazil

4. Institute for Advanced Studies of Ocean, UNESP, São Vicente, Brazil

5. Departamento de Patologia, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil

6. Centro de Ciências Naturais e Humanas, Universidade Federal do ABC, Santo André, Brazil

7. Instituto de Química, Universidade Federal de Alfenas, Alfenas, Brazil

8. Instituto de Química, Universidade Federal Fluminense, Niterói, Brazil

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. 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.

Funder

Fundação de Amparo à Pesquisa do Estado de São Paulo - FAPESP

Conselho Nacional de Desenvolvimento Científico e Tecnológico - CNPq

Publisher

Bentham Science Publishers Ltd.

Subject

Drug Discovery,General Medicine

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