The Noscapine Chronicle: A Pharmaco‐Historic Biography of the Opiate Alkaloid Family and its Clinical Applications

Abstract

Given its manifold potential therapeutic applications and amenability to modification, noscapine is a veritable “Renaissance drug” worthy of commemoration. Perhaps the only facet of noscapine’s profile more astounding than its versatility is its virtual lack of side effects and addictive properties, which distinguishes it from other denizens of Papaver somniferum. This review intimately chronicles the rich intellectual and pharmacological history behind the noscapine family of compounds, the length of whose arms was revealed over decades of patient scholarship and experimentation. We discuss the intriguing story of this family of nontoxic alkaloids, from noscapine’s purification from opium at the turn of the 19th century in Paris to the recent torrent of rationally designed analogs with tremendous anticancer potential. In between, noscapine’s unique pharmacology; impact on cellular signaling pathways, the mitotic spindle, and centrosome clustering; use as an antimalarial drug and cough suppressant; and exceptional potential as a treatment for polycystic ovarian syndrome, strokes, and diverse malignancies are catalogued. Seminal experiments involving some of its more promising analogs, such as amino-noscapine, 9-nitronoscapine, 9-bromonoscapine, and reduced bromonoscapine, are also detailed. Finally, the bright future of these oftentimes even more exceptional derivatives is described, rounding out a portrait of a truly remarkable family of compounds.

Heterodimeric O‐methyltransferases involved in the biosynthesis of noscapine in opium poppy

“…Noscapine is a benzylisoquinoline alkaloid (BIA) in the phthalide isoquinoline structural category that has long been used as a cough suppressant and investigated as a potential anticancer drug (Rida et al ., ). Noscapine is generally the second most abundant alkaloid after morphine in opium poppy ( Papaver somniferum ), but unlike opiate alkaloids noscapine does not possess analgesic or narcotic properties (Chen et al ., ).…”

Noscapine chemosensitization enhances docetaxel anticancer activity and nanocarrier uptake in triple negative breast cancer

“…Natural compounds have been explored to act as potent chemo-sensitizers in combination with conventional chemotherapeutic drugs and are pharmacologically safe over several synthetic chemicals due to low systemic toxicity [6,7]. Noscapine (Nos) is a commonly used cough suppressant, and has been extensively investigated as a single agent anticancer therapy against melanoma, lung, prostate, ovarian and breast cancers and works by acting on microtubules like taxanes, inducing apoptosis and inhibiting angiogenesis [8–11].…”

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“…Noscapine improves radiation sensitivity of gliomas, causing a significant growth delay and a decrease in tumor vessel density and tubule formation; hence, this drug may prove especially useful in glioblastoma patients who are candidates for radiation therapy. [8] …”