| Full text | |
| Author(s): |
Brito, Ivanildo A.
;
Levatti, Erica V. Castro
;
Regasini, Luis O.
;
Ferreira, Edgard A.
;
Lopes, Flavia B.
;
Fernandes, Joao Paulo S.
;
Batista Jr, Joao M.
;
Tempone, Andre G.
;
Lago, Joao Henrique G.
Total Authors: 9
|
| Document type: | Journal article |
| Source: | Phytochemistry; v. 231, p. 10-pg., 2024-12-17. |
| Abstract | |
As part of our continuous study on the Annonaceae species Porcelia macrocarpa, in the present work, eight chemically related 2-alkyl-3-hydroxy-4-methyl-gamma-lactones (1-8) were isolated. Their structures were characterised by NMR, MS, and VCD. Their antitrypanosomal activity was evaluated in vitro against intracellular amastigotes with EC50 values ranged from 13.9 to 1.1 mu M for compounds 1-3 and 6-8, while compounds 4 and 5 were inactive (EC50 > 100 mu M). Compounds 1-8 did not exert toxicity against NCTC cells at the highest tested concentration (CC50 > 200 mu M). Compared with the standard drug benznidazole (EC50 = 3.6 mu M and SI > 54.6), compound 8 proved to be the most potent gamma-lactone with an EC50 of 1.1 mu M and an SI of >181.8. Finally, the structure-activity relationship analysis suggested that flexibility and length of side chain of the related gamma-lactones 1-8 play an important role in the activity against amastigotes. The results contribute to the discovery of new molecular prototypes that can be used as scaffolds for developing drugs to treat Chagas disease. (AU) | |
| FAPESP's process: | 23/12447-1 - Searching for specialized metabolites from Brazilian floristic biodiversity as drug candidates for neglected tropical diseases |
| Grantee: | João Henrique Ghilardi Lago |
| Support Opportunities: | BIOTA-FAPESP Program - Regular Research Grants |
| FAPESP's process: | 23/12475-5 - Systematizing chiroptical properties of lignans: implications for correct absolute configuration assignments |
| Grantee: | João Marcos Batista Junior |
| Support Opportunities: | 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 |