Insight into the Tubulin-Targeted Anticancer Potential of Noscapine and its Structural Analogs

Abstract

Abstract: Cancer is known as a notorious disease responsible for threatening millions of lives every year. Natural products which act by disrupting the microtubule assembly and dynamics have proven to be highly successful as anticancer agents but their high toxicity owing to lower selectivity has limited their usage. Recently, Noscapine (NOS), a known anti-tussive, has come out to be an effective anti-tubulin candidate with far lesser toxicity. Since its first report as an anti-mitotic agent in 1998, NOS has been extensively studied and modified by various groups of researchers to optimize its anti-tubulin activity. In this review, the recent advancements about the potential of these therapeutic candidates against various cancers have been compiled and analyzed for their inhibitory mechanism in distinct health conditions. It has been observed that the non-polar substitutions (e.g., halides, aryl groups) at specific sites (9-position and N-sites of isoquinoline ring; and modification of a methoxy group) have an enhanced effect on efficacy. The mechanistic studies of NOS and its modified analogs have shown their inhibitory action primarily through interaction with microtubules dynamics thus disrupting the cell-cycle and leading to apoptosis. This review highlights the latest research in the field by providing a rich resource for the researchers to have a hands-on analysis of NOS analogs and the inhibitory action in comparison to other microtubule disrupting anti-cancer agents. The article also documents the newer investigations in studying the potential of noscapine analogs as possible anti-microbial and antiviral agents.