Development of novel benzofuran-isatin conjugates as potential antiproliferative agents with apoptosis inducing mechanism in Colon cancer.
J Enzyme Inhib Med Chem
; 36(1): 1424-1435, 2021 Dec.
Article
em En
| MEDLINE
| ID: mdl-34176414
ABSTRACT
In the current work, a new set of carbohydrazide linked benzofuran-isatin conjugates (5a-e and 7a-i) was designed and synthesised. The anticancer activity for compounds (5b-d, 7a, 7b, 7d and 7g) was measured against NCI-55 human cancer cell lines. Compound 5d was the most efficient, and thus subjected to the five-dose screen where it showed excellent broad activity against almost all tested cancer subpanels. Furthermore, all conjugates (5a-e and 7a-i) showed a good anti-proliferative activity towards colorectal cancer SW-620 and HT-29 cell lines, with an excellent inhibitory effect for compounds 5a and 5d (IC50 = 8.7 and 9.4 µM (5a), and 6.5 and 9.8 µM for (5d), respectively). Both compounds displayed selective cytotoxicity with good safety profile. In addition, both compounds provoked apoptosis in a dose dependent manner in SW-620 cells. Also, they significantly inhibited the anti-apoptotic Bcl2 protein expression and increased the cleaved PARP level that resulted in SW-620 cells apoptosis.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Benzofuranos
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Apoptose
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Neoplasias do Colo
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Proliferação de Células
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Isatina
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Antineoplásicos
Limite:
Humans
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article