title: Synthesis and evaluation of polymeric gold glyco-conjugates as anti-cancer agents.
abstract: The antitumor activity of organo-gold compounds is a focus of research from the past two decades. A variety of gold stabilizing ligands such as vitamins and xanthanes have been prepared and explored for their 'chelating effect' as well as for their antitumor activity. Dithiocarbamates (DTC) compounds and their metallic conjugates have been well explored for their antiproliferative activities. In this study, glycopolymer based DTC-conjugates are prepared by reversible addition-fragmentation chain transfer polymerization (RAFT) and subsequently modified with gold(I) phosphine. These polymer-DTC derivatives and their gold compounds are tested for their in vitro toxicity in both normal and cancer cell lines. The Au(I) phosphine conjugated cationic glycopolymers of 10 kDa and 30 kDa are evaluated for their cytotoxicity profiles using MTT assay. Au(I) compounds are well-known for their mitochondrial toxicity, hence hypoxic cell lines bearing unusually enlarged mitochondria are subjected to these anticancer compounds. It is concluded that these polymeric DTC derivatives and their gold conjugates indeed show higher accumulation as well as cytotoxicity to cancer cells under hypoxic conditions in comparison to the normoxic ones. Hypoxic MCF-7 cells showed significant sensitivity toward the low molecular weight (10 kDa) glycopolymer-Au(I) complexes.
authors: Department of Chemical and Materials Engineering, Alberta Glycomics Centre, University of Alberta, Edmonton, AB, T6G 2G6, Canada.
authors: Marya
authors: M
authors: Ahmed
authors: Saul
authors: S
authors: Mamba
authors: Xiao-Hong
authors: XH
authors: Yang
authors: James
authors: J
authors: Darkwa
authors: Piyush
authors: P
authors: Kumar
authors: Ravin
authors: R
authors: Narain
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002241:Carbohydrates / Q000737:chemistry*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D005347:Fibroblasts / Q000187:drug effects; D006046:Gold / Q000737:chemistry*; D057809:HEK293 Cells; D056945:Hep G2 Cells; D006801:Humans; D061986:MCF-7 Cells; D015394:Molecular Structure; D008970:Molecular Weight; D050607:Organogold Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011108:Polymers / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D012867:Skin / Q000166:cytology / Q000187:drug effects; D013329:Structure-Activity Relationship; D013859:Thiocarbamates / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D002241:Carbohydrates; D050607:Organogold Compounds; D011108:Polymers; D013859:Thiocarbamates; D006046:Gold