Noscapine is an alkaloid with a basic phthalideisoquinoline moiety and is well recognized as an antitussive drug. It is obtained from opium poppy Papaver somniferum and demonstrates a rather safe toxicity profile in vitro. Recent studies found noscapine and its analogues to have anticancer activity against mammalian cancer cell lines by modulating microtubule assembly. In the present study, we report the synthesis and evaluation of cytotoxicity of a series of N-sulfonyl noscapinoids 6a-n obtained by reaction of nornoscapine with various aryl/heteroaryl sulfonyl chlorides. To assess the anti-proliferative activity of the novel derivatives 6a-n, SRB assay was performed in four different human cancer cell lines, MIAPaCa-2 (pancreatic), HeLa (cervical), SK N SH (neuroblastoma) and DU145 (prostate cancer). The study identified four compounds 6e-g and 6j ability to arrest cell-cycle at the G2/M phase and cytotoxic potential against the human pancreatic cancer cell line MIAPaCa-2. We observed that these compounds 6e-g and 6j induce microtubule depolymerisation and cause cell cycle arrest at the G2/M phase thereby resulting in caspase-3 and PARP activation leading to cell death. In silico molecular docking studies of these compounds showed non-covalent interactions like Van der Waals and hydrogen-bonding with tubulin protein and with good binding energy.