title: Synthesis of artemisinin dimers using the Ugi reaction and their in vitro efficacy on breast cancer cells.
abstract: The Ugi four-component reaction was used to prepare a series of artemisinin monomers and dimers. We found that the endoperoxide group in artemisinin remains intact during the reaction. The new artemisinin dimers showed potent anti-cancer activity against two human breast cancer cell lines, MDA-MB-231 and BT-474. One of the Ugi artemisinin dimers showed an IC₅₀ value of 12 nM when tested on BT474 cells, more than 600 times more potent than artesunate. Furthermore, the same Ugi artemisinin dimer showed a low toxicity when tested on MCF10A, a nontumorigenic cell line, resulting in a selectivity index of more than 8000.
authors.affiliation: Department of Chemistry, University of Washington, Box 351700, Seattle, WA 98195-1700, USA.
authors.forename: Shusheng
authors.initials: S
authors.lastname: Wang
authors.forename: Tomikazu
authors.initials: T
authors.lastname: Sasaki
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D037621:Artemisinins / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D001943:Breast Neoplasms / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D019281:Dimerization; D005260:Female; D006801:Humans
chemical_list: D000970:Antineoplastic Agents; D037621:Artemisinins; C031327:artemisinin