Discovery of N-Ts-3-benzylidene-indolin-2-imines as potent anti-colorectal cancer agents through suppression of the PI3K-AKT pathway

Colorectal Cancer (CRC) is among the most prevalent and aggressive malignancies, highlighting the urgent need for novel therapeutic agents. In this study, eleven N-Ts-3-benzylidene-indolin-2-imines 3 were synthesized and evaluated for their potential as novel anti-tumor agents. MTT assay in human colorectal, breast, lung, and liver Cancer cell lines revealed that compound 3h, bearing a methoxyl group, exhibited superior antiproliferative activity against SW620 cells, with an IC₅₀ value of 3.68 μM. The above compound was subsequently selected for further investigation of its anti-CRC activity. This compound effectively inhibited colony formation and induced G2/M arrest and Apoptosis in SW620 cells. Western blot analysis further demonstrated that 3h exerted its anti-tumor activity by blocking the PI3K-AKT signaling pathway. Moreover, potential binding modes of compound 3h with several PI3K and Akt kinases were proposed using molecular docking studies. This is the first report to describe the Anticancer activity of indolin-2-imines through the suppression of the PI3K-AKT pathway. Overall, our findings suggested that compound 3h is a promising lead for the development of PI3K/Akt inhibitors and anti-CRC agents.

Colorectal cancer; Indole; Indolin-2-imine; Indoline; PI3K-AKT.