Dithiocarbamation of spiro-aziridine oxindoles: a facile access to C3-functionalised 3-thiooxindoles as apoptosis inducing agents

Herein, we report the first dithiocarbamation of spiro-aziridine oxindoles involving regiospecific ring-opening by using in situ generated nucleophilic dithiocarbamates as an instant source of sulfur. This approach afforded C3-functionalised-3-thiooxindoles in good to excellent yields with a wide substrate scope under catalyst-free and mild reaction conditions. These compounds were screened for their anticancer activity against a panel of human cancer cell lines, wherein compound 3u exhibited significant cytotoxic activity against human lung cancer cells with an IC 50 value of 4.31 ± 1.88 μM. Phase contrast microscopy as well as different staining assays such as acridine orange/ethidium bromide (AO/EB), DAPI and DCFDA demonstrated the induction of apoptosis in A549 lung cancer cells after treatment with compound 3u . In addition, the clonogenic assay and migration assay demonstrated the ability of compound 3u to inhibit colony formation and cell migration, respectively, in A549 cells in a dose-dependent manner. An efficient access to C3-functionalised 3-thiooxindoles has been accomplished via direct dithiocarbamation of spiro-aziridine oxindoles. Their apoptosis-inducing properties have been investigated.