Taking aim at a dynamic target: Noscapinoids as microtubule-targeted cancer therapeutics

Abstract

Noscapine and its synthetic derivatives called noscapinoids have been shown to possess potential anticancer properties. These alkaloids target microtubules and inhibit cell proliferation. Noscapinoids are microtubule poisons that induce minor alterations in the innate dynamic instability of microtubules leading to mitotic arrest and cell death. Over the past decade, a number of noscapine derivatives have been synthesized that, compared to the parent compound, show superior anticancer potential, enhanced tumor specificity and tumor regression, and little or no toxicity to normal tissues. Based on their successive synthetic modifications at different points in the scaffold structure of noscapine, aided by computational design and structure-activity relationship studies, the derivatives of noscapine have been classified into different "generations" based on modifications. Several studies have reported the potential to develop noscapinoids as anticancer drugs. Increasing their tumor specificity - either through antibody conjugation or nanoparticle-based carriers - may facilitate the progression of maytansinoid-based cancer drugs to the clinic.

Keywords: Anticancer agents; Microtubule; Noscapine; Noscapinoids; Tubulin.