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
(IC
50
= 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.