The Therapeutic Potential of Migrastatin-Core Analogs for the Treatment of Metastatic Cancer

Abstract

Tumor metastasis is a complex process in which cells detach from the primary tumor and colonize a distant organ. Metastasis is also the main process responsible for cancer-related death. Despite the enormous efforts made to unravel the metastatic process, there is no effective therapy, and patients with metastatic tumors have poor prognosis. In this regard, there is an urgent need for new therapeutic tools for the treatment of this disease. Small molecules with the capacity to reduce cell migration could be used to treat metastasis. Migrastatin-core analogs are naturally inspired macrocycles that inhibit pathological cell migration and are able to reduce metastasis in animal models. Migrastatin analogs can be synthesized from a common advanced intermediate. Herein we present a review of the synthetic approaches that can be used to prepare this key intermediate, together with a review of the biological activity of migrastatin-core analogs and current hypotheses concerning their mechanism of action.

Knockout of glucosidase II beta subunit inhibits growth and metastatic potential of lung cancer cells by inhibiting receptor tyrosine kinase activities

“…Cell migration and anchorage independent growth are fundamental components of tumor cell metastasis 8 . To assess the effect of GluIIβ on cell mobility, we examined the migration of GluIIβ knockout cells and their corresponding control using the transwell migration assay 9,10 . Figure 3A shows representative migrated cells stained with crystal violet examined after 16 hours of incubation.…”

Total Synthesis of a Hypothetical Macroketone of Migrastatin

“…Cancer metastasis accounts for more than 95 % of deaths due to cancer [3] . Actin is one of the major cytoskeletal components in the process of cell migration [4] where polymeric actin filaments assemble via a process called actin bundling, and results in the formation of cellular structures like filopodial, which in turn assists in cell migra‐tion [5] . This actin polymerization process is controlled by a specific actin bundling protein called fascin [6] .…”

Bioactive Streptoglutarimides A–J from the Marine-Derived Streptomyces sp. ZZ741

“…The earliest reported glutarimide antibiotics are the streptovitacins, , and their most well-known member is cycloheximide, an inhibitor of eukaryotic translation and the most commonly used reagent for inhibiting protein synthesis . Based on their property of inhibiting the translation of eukaryotic cells, some glutarimide antibiotics show potential for the development of antitumor , and antiviral drug leads. For example, migrastatin, produced by Streptomyces sp.…”

“…For example, migrastatin, produced by Streptomyces sp. MK929-43F1, was found to inhibit tumor cell migration and has served as an antimetastatic drug lead . The biosynthesis of certain glutarimide members, such as actiphenol, cycloheximide, isomigrastatin, , lactimidomycin, , migrastatin, , and 9-methylstreptimidone, has been well investigated.…”