Dissecting the mitochondrial oxidative defense of Trypanosoma cruzi
| Full text | |
| Author(s): |
Brito, Juliana R.
[1]
;
Da Costa-Silva, Thais A.
[2]
;
Tempone, Andre G.
[3]
;
Ferreira, Edgard A.
[4]
;
Lago, Joao Henrique G.
[2]
Total Authors: 5
|
| Affiliation: | [1] Univ Fed Sao Paulo, Inst Environm Chem & Pharmaceut Sci, BR-09972270 Diadema, SP - Brazil
[2] Fed Univ ABC, Ctr Nat Sci & Humanities, BR-09210180 Santo Andre, SP - Brazil
[3] Adolfo Lutz Inst, Ctr Parasitol & Mycol, BR-01246902 Sao Paulo, SP - Brazil
[4] Univ Prebiteriana Mackenzie, Sch Engn, BR-01302907 Sao Paulo, SP - Brazil
Total Affiliations: 4
|
| Document type: | Journal article |
| Source: | Fitoterapia; v. 137, SEP 2019. |
| Web of Science Citations: | 0 |
| Abstract | |
The MeOH extract from leaves of Saururus cernuus L. (Saururaceae) displayed in vitro activity against trypomastigote forms of T. cruzi (100% of parasite death at 200 mu g/mL), suggesting the presence of bioactive compounds. Thus, the bioactivity-guided fractionation was carried out, leading to the isolation of three related neolignan derivatives, identified as threo-austrobailignan-5 (1), threo-austrobailignan-6 (2), and threo-dihydroguaiaretic acid (3). Anti-T. cruzi activity of compounds 1-3 was performed against cell-derived trypomastigotes and intracellular amastigotes. Additionally, the mammalian cytotoxicity was investigated using NCTC cells. Compound 2 was the most effective against extracellular trypomastigotes with IC50 of 3.7 mu M, while compound 3 showed activity in both clinically relevant forms of the parasite, trypomastigotes and amastigotes, with IC50 values of 7.0 and 16.2 mu M, respectively. However, the structurally related compound 1 was inactive. Based on these results, compounds 2 and 3 were selected to evaluate the mechanism of cellular death. Compound 2 induced alteration in the plasma membrane permeability and consequently in the ROS levels after 120 min of incubation. By using flow cytometry and fluorescence microscopy, compound 3 showed alterations in the mitochondrial membrane potential (Delta psi(m)) of trypomastigotes. Considering the promising chemical and biological properties of neolignans 2 and 3, these compounds could be used as starting points to develop new lead compounds for Chagas disease. (AU) | |
| FAPESP's process: | 18/10279-6 - Selection and optimization of new drug candidates for Leishmaniasis and Chagas Disease |
| Grantee: | André Gustavo Tempone Cardoso |
| Support type: | Regular Research Grants |
| FAPESP's process: | 18/07885-1 - Biomolecules from plant species of remnant areas of the Atlantic Forest and Cerrado to treat neglected tropical diseases - chemical and pharmacological aspects |
| Grantee: | João Henrique Ghilardi Lago |
| Support type: | BIOTA-FAPESP Program - Regular Research Grants |