Anticancer Potential of N‐Sulfonyl Noscapinoids: Synthesis and Evaluation

Abstract

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 6 a–n obtained by reaction of nornoscapine with various aryl/heteroaryl sulfonyl chlorides. To assess the antiproliferative activity of the novel derivatives 6 a–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 6 e–g and 6 j 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 6 e–g and 6 j 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.

Identification of novel anti-cancer agents by the synthesis and cellular screening of a noscapine-based library

“…7 The chemical structure of noscapine consists of an isoquinoline and a phthalide moiety. There are many studies in the literature reporting the chemical modification of noscapine scaffold, including the methyl-residue of the isoquinoline moiety, 9,10 modification of the phthalide moiety, 11 and of both parts. 12,13 Noscapine derivatives with modifications at the positions 1, 6, 7 and 9 were reported (Fig.…”