Benzothienoquinazolinones as new multi-target scaffolds: Dual inhibition of human Topoisomerase I and tubulin polymerization.
Eur J Med Chem
; 181: 111583, 2019 Nov 01.
Article
em En
| MEDLINE
| ID: mdl-31400710
ABSTRACT
3-(Alkyl(dialkyl)amino)benzothieno[2,3-f]quinazolin-1(2H)-ones (4-9) have been designed using Ellipticine structure as a model, replacing the carbazole core and the pyridine ring with a dibenzothiophene and a pyrimidine moiety, respectively. New benzothienoquinazolinones (4-9) have been synthesized by a simple one-pot reaction employing 3-aminodibenzothiophene as starting material. The benzothienoquinazolinones obtained (4-9), were evaluated for their anticancer activity against two breast cancer cell lines, MDA-MB-231 and MCF-7. The results revealed that compounds 4 and 7 presented a good antitumor activity toward the triple negative MDA-MB-231, without cytotoxicity against non-tumoral cells. Furthermore, the compounds 4 and 7 can be considered important molecular multi-target tools for their dual inhibition of different cellular proteins, i.e. Tubulin and human Topoisomerase I, involved in relevant cellular processes, as predicted by in silico studies and demonstrated by in vitro assays (for compound 4).
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Tubulina (Proteína)
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DNA Topoisomerases Tipo I
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Moduladores de Tubulina
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Inibidores da Topoisomerase I
Tipo de estudo:
Prognostic_studies
Limite:
Female
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Humans
Idioma:
En
Revista:
Eur J Med Chem
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Itália