Biodiversity and areas of endemism of benthic hydroids (Cnidaria, Hydrozoa) from s...
| Full text | |
| Author(s): |
Lima, Marta L.
[1]
;
Romanelli, Maiara M.
[1]
;
Borborema, Samanta E. T.
[1]
;
Johns, Deidre M.
[2]
;
Migotto, Alvaro Esteves
[3]
;
Lago, Joao Henrique G.
[4]
;
Tempone, Andre G.
[1]
Total Authors: 7
|
| Affiliation: | [1] Adolfo Lutz Inst, Ctr Parasitol & Mycol, Ave Dr Arnaldo 351, 8 Andar, BR-01246000 Sao Paulo - Brazil
[2] Oregon State Univ, Dept Biomed Sci, Corvallis, OR 97331 - USA
[3] Univ Sao Paulo, Ctr Biol Marinha, Sao Sebastiao - Brazil
[4] Fed Univ ABC UFABC, Ctr Nat Sci & Humanities, BR-09210580 Santo Andre - Brazil
Total Affiliations: 4
|
| Document type: | Journal article |
| Source: | BIOORGANIC CHEMISTRY; v. 89, AUG 2019. |
| Web of Science Citations: | 2 |
| Abstract | |
Marine invertebrates are a rich source of small antiparasitic compounds. Among them, Macrorhynchia philippina is a chemically underexplored marine cnidarian. In the search for candidates against the neglected protozoan Chagas disease, we performed a bio-guided fractionation to obtain active compounds. The structural characterization of the active compound was determined using NMR analysis and MS and resulted in the isololiolide, a compound described for the first time in this species. It showed in vitro activity against both trypomastigote and intracellular amastigotes of Trypanosoma cruzi, with IC50, values of 32 mu M and 40 mu M, respectively, with no mammalian cytotoxicity ( > 200 mu M). The lethal action was investigated in T. cruzi using different fluorophores to study: (i) mitochondrial membrane potential; (ii) plasma membrane potential and (iii) plasma membrane permeability. Our results demonstrated that isololiolide caused disruption of the plasma membrane integrity and a strong depolarization of the mitochondrial membrane potential, rapidly leading the parasite to death. Despite being considered a possible covalent inhibitor, safety in silico studies of isololiolide also considered neither mutagenic nor genotoxic potential. Additionally, isololiolide showed no resemblance to interference compounds (PAINS), and it succeeded in most filters for drug-likeness. Isololiolide is a promising candidate for future optimization against 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 |