| Full text | |
| Author(s): |
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
Total Authors: 9
|
| Document type: | Journal article |
| Source: | CURRENT TOPICS IN MEDICINAL CHEMISTRY; v. 22, n. 19, p. 8-pg., 2022-01-01. |
| 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 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) | |
| FAPESP's process: | 18/24077-6 - Pre-clinical studies of non-invasive treatments in leishmaniasis |
| Grantee: | Luiz Felipe Domingues Passero |
| Support Opportunities: | Regular Research Grants |
| FAPESP's process: | 21/02789-7 - Search for bioactive metabolites with antiparasitic action in plant species from Atlantic Forest and Cerrado regions - a chemical, phenotypical, and metabolomic approach |
| Grantee: | João Henrique Ghilardi Lago |
| Support Opportunities: | BIOTA-FAPESP Program - Regular Research Grants |
| FAPESP's process: | 19/22319-5 - Vibrational circular dichroism spectral markers: facilitating absolute configuration assignment of natural products |
| Grantee: | João Marcos Batista Junior |
| Support Opportunities: | Regular Research Grants |
| FAPESP's process: | 16/24985-4 - Study the chemical composition of fungi and plants of the Atlantic Forest aimed at antitumor, antiparasitic and antimicrobial potential |
| Grantee: | Patricia Sartorelli |
| Support Opportunities: | Regular Research Grants |