Alvaxanthone, a Thymidylate Synthase Inhibitor with Nematocidal and Tumoricidal Activities.
Molecules
; 25(12)2020 Jun 23.
Article
em En
| MEDLINE
| ID: mdl-32586022
ABSTRACT
With the aim to identify novel inhibitors of parasitic nematode thymidylate synthase (TS), we screened in silico an in-house library of natural compounds, taking advantage of a model of nematode TS three-dimensional (3D) structure and choosing candidate compounds potentially capable of enzyme binding/inhibition. Selected compounds were tested as (i) inhibitors of the reaction catalyzed by TSs of different species, (ii) agents toxic to a nematode parasite model (C. elegans grown in vitro), (iii) inhibitors of normal human cell growth, and (iv) antitumor agents affecting human tumor cells grown in vitro. The results pointed to alvaxanthone as a relatively strong TS inhibitor that causes C. elegans population growth reduction with nematocidal potency similar to the anthelmintic drug mebendazole. Alvaxanthone also demonstrated an antiproliferative effect in tumor cells, associated with a selective toxicity against mitochondria observed in cancer cells compared to normal cells.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Timidilato Sintase
/
Xantonas
/
Inibidores Enzimáticos
/
Antinematódeos
/
Antineoplásicos
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article