title: 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.
authors.affiliation: Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, C/Baldiri Reixac 10, Barcelona E-08028, Spain. ernest.giralt@irbbarcelona.org.|Department of Organic Chemistry, University of Barcelona, Marti i Franques 1-11, Barcelona E-08028, Spain. ernest.giralt@irbbarcelona.org.
authors.forename: Ernest
authors.initials: E
authors.lastname: Giralt
authors.affiliation: Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, C/Baldiri Reixac 10, Barcelona E-08028, Spain. daniele.lore@irbbarcelona.org.
authors.forename: Daniele
authors.initials: D
authors.lastname: Lo Re
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use; D001688:Biological Products / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D004353:Drug Evaluation, Preclinical; D006801:Humans; D018942:Macrolides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D010881:Piperidones / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D001688:Biological Products; D018942:Macrolides; D010881:Piperidones; C418199:migrastatin
keywords: cancer metastasis; diverted total synthesis; natural products