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

Autor(es)

Monteiro, Jackson ; Passero, Luiz Felipe D. ; Jesus, Jessica A. ; Laurenti, Marcia D. ; Lago, Joao H. G. ; Soares, Marisi G. ; Batista, Andrea N. L. ; Batista Jr, Joao M. ; Sartorelli, Patricia

• Tipo de documento: Artigo Científico
• Fonte: CURRENT TOPICS IN MEDICINAL CHEMISTRY; v. 22, n. 19, p. 8-pg., 2022-01-01.

Resumo

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 mu M, respectively. Furthermore, this compound was non-toxic in J774 macrophage cells (CC50 > 458.71 mu M) 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. (AU)

• Processo FAPESP: 18/24077-6 - Estudos pré-clínicos de tratamentos não invasivos nas leishmanioses
• Beneficiário: Luiz Felipe Domingues Passero
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 21/02789-7 - Busca de metabólitos bioativos com ação antiparasitária em espécies vegetais de regiões de Mata Atlântica e Cerrado - uma abordagem química, fenotípica e metabolômica
• Beneficiário: João Henrique Ghilardi Lago
• Modalidade de apoio: Auxílio à Pesquisa - Programa BIOTA - Regular
• Processo FAPESP: 19/22319-5 - Marcadores espectrais de dicroísmo circular vibracional: facilitando o assinalamento da configuração absoluta de produtos naturais
• Beneficiário: João Marcos Batista Junior
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 16/24985-4 - Estudo da composição química de fungos e plantas da Mata Atlântica visando o potencial antitumoral, antiparasitário e antimicrobiano
• Beneficiário: Patricia Sartorelli
• Modalidade de apoio: Auxílio à Pesquisa - Regular