Development of novel benzofuran-isatin conjugates as potential antiproliferative agents with apoptosis inducing mechanism in Colon cancer

Abstract

In the current work, a new set of carbohydrazide linked benzofuran-isatin conjugates (<b>5a-e</b> and <b>7a-i</b>) was designed and synthesised. The anticancer activity for compounds (<b>5b-d</b>, <b>7a, 7b, 7d</b> and <b>7g</b>) was measured against NCI-55 human cancer cell lines. Compound <b>5d</b> 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 (<b>5a-e</b> and <b>7a-i</b>) showed a good anti-proliferative activity towards colorectal cancer SW-620 and HT-29 cell lines, with an excellent inhibitory effect for compounds <b>5a</b> and <b>5d</b> (IC₅₀ = 8.7 and 9.4 µM (<b>5a</b>), and 6.5 and 9.8 µM for (<b>5d</b>), 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.