Development of noscapine congener for the management of breast cancer

Abstract

Drugs that target mitotic spindle, such as taxol, vinca-drugs, and estramustine have newlinebeen in the clinic for the treatment of different types of breast cancers. However, these newlinedrugs are known to cause severe dose-limiting toxicities in patients such as peripheral newlineneuropathy, systemic toxicity, and allergic reactions. More importantly patients are newlinedeveloping resistance against taxol. Thus, wonderful promise of taxol in managing breast newlinecancers justifies further effort to discover novel mitotic inhibitors. Better yet, it would be additionally useful if other novel anti-mitotic agents have less side effects and easily administered. Our initial efforts towards this end have been quite encouraging in that we have rationally designed and chemically synthesized a battery of derivatives of natural lead molecule, Noscapine (opium alkaloid, used as anticough medicine and identified as tubulin binding anticancer agent). Some of these compounds were demonstrated as more newlinepotent compared to Noscapine as anticancer agent. In a quest of making novel derivatives newlineof noscapine, the present study focusing on rational design of five new classes of newlinenoscapinoids such as (1) 1,3-diynyl-noscapinoids, (2) 9-arylimino noscapinoids, (3) Narylalkylamino-noscapinoids, (4) N-imidazopyridine-noscapinoids and (5) 9-Urea newlinenoscapinoids, followed by chemical synthesis and exhaustive experimental evaluation as newlinepotent anticancer agents with little or no toxicity that holds great promise for clinical use.