title: Novel Colchicine Derivatives and their Anti-cancer Activity.
abstract: In this paper we provide an overview of the status of various colchicine derivatives in preclinical development with special focus on their anti-cancer activity. We discuss several groups of compounds that have been designed to differentially bind with specific affinities for tubulin β isotypes, especially in regard to βIII, which is commonly over-expressed in cancer. Computational prediction, protein-based and cell-based assays are summarized as well as some animal tests conducted on these compounds. It is concluded that an untapped potential exists for exploiting the colchicine scaffold as a pharmacophore with the possibility of increasing its affinity for tubulin isotypes overexpressed in cancer and decreasing it for normal cells thereby widening the therapeutic window.
authors.affiliation: Department of Oncology, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Lorelei
authors.initials: L
authors.lastname: Johnson
authors.affiliation: Department of Biochemistry, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Ing Swie
authors.initials: IS
authors.lastname: Goping
authors.affiliation: Department of Biochemistry, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Aja
authors.initials: A
authors.lastname: Rieger
authors.affiliation: Department of Oncology, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Jonathan Y
authors.initials: JY
authors.lastname: Mane
authors.affiliation: Department of Oncology, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Torin
authors.initials: T
authors.lastname: Huzil
authors.affiliation: Department of Biochemistry, University of Texas Health Science Center at San Antonio, San Antonio, TX 78240. United States.
authors.forename: Asok
authors.initials: A
authors.lastname: Banerjee
authors.affiliation: Department of Biochemistry, University of Texas Health Science Center at San Antonio, San Antonio, TX 78240. United States.
authors.forename: Richard
authors.initials: R
authors.lastname: Luduena
authors.affiliation: Department of Oncology, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Bashar
authors.initials: B
authors.lastname: Hassani
authors.affiliation: Department of Oncology, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Philip
authors.initials: P
authors.lastname: Winter
authors.affiliation: Department of Oncology, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Jack A
authors.initials: JA
authors.lastname: Tuszynski
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D003078:Colchicine / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D014404:Tubulin / Q000235:genetics / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D014404:Tubulin; D003078:Colchicine
keywords: Animal tests; Anti-cancer; Colchicine Scaffold; Pharmacophore; Tubulin β isotypes