Phenolic thio- and selenosemicarbazones as multi-target drugs.
Eur J Med Chem
; 94: 63-72, 2015 Apr 13.
Article
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| MEDLINE
| ID: mdl-25752525
ABSTRACT
A series of isosteric phenolic thio- and selenosemicarbazones have been obtained by condensation of naturally-occurring phenolic aldehydes and thio(seleno)semicarbazides. Title compounds were designed as potential multi-target drugs, and a series of structure-activity relationships could be established upon their in vitro assays antioxidant activity, α-glucosidase inhibition and antiproliferative activity against six human tumor cell lines A549 (non-small cell lung), HBL-100 (breast), HeLa (cervix), SW1573 (non-small cell lung), T-47D (breast) and WiDr (colon). For the antiradical activity, selenium atom and 2 or 3 phenolic hydroxyl groups proved to be essential motifs; remarkably, the compound with the most potent activity, with a trihydroxyphenyl scaffold (EC50 = 4.87 ± 1.57 µM) was found to be stronger than natural hydroxytyrosol, a potent antioxidant present in olive oil (EC50 = 13.80 ± 1.41 µM). Furthermore, one of the thiosemicarbazones was found to be a strong non-competitive inhibitor of α-glucosidase (Ki = 9.6 ± 1.6 µM), with an 8-fold increase in activity compared to acarbose (Ki = 77.9 ± 11.4 µM), marketed for the treatment of type-2 diabetes. Most of the synthesized compounds also exhibited relevant antiproliferative activities; in particular, seleno derivatives showed GI50 values lower than 6.0 µM for all the tested cell lines; N-naphthyl mono- and dihydroxylated derivatives behaved as more potent antiproliferative agents than 5-fluorouracil or cisplatin.
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Bases de datos:
MEDLINE
Asunto principal:
Relación Estructura-Actividad
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Inhibidores de Glicósido Hidrolasas
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Antineoplásicos
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Antioxidantes
Idioma:
En
Revista:
Eur J Med Chem
Año:
2015
Tipo del documento:
Article
País de afiliación:
España