title: Synthesis of new cytotoxic aminoanthraquinone derivatives via nucleophilic substitution reactions.
abstract: Aminoanthraquinones were successfully synthesized via two reaction steps. 1,4-Dihydroxyanthraquinone (1) was first subjected to methylation, reduction and acylation to give an excellent yield of anthracene-1,4-dione (3), 1,4-dimethoxyanthracene-9,10-dione (5) and 9,10-dioxo-9,10-dihydroanthracene-1,4-diyl diacetate (7). Treatment of 1, 3, 5 and 7 with BuNH2 in the presence of PhI(OAc)2 as catalyst produced seven aminoanthraquinone derivatives 1a, b, 3a, and 5a-d. Amination of 3 and 5 afforded three new aminoanthraquinones, namely 2-(butylamino)anthracene-1,4-dione (3a), 2-(butylamino)anthracene-9,10-dione (5a) and 2,3-(dibutylamino)anthracene-9,10-dione (5b). All newly synthesised aminoanthraquinones were examined for their cytotoxic activity against MCF-7 (estrogen receptor positive human breast) and Hep-G2 (human hepatocellular liver carcinoma) cancer cells using MTT assay. Aminoanthraquinones 3a, 5a and 5b exhibited strong cytotoxicity towards both cancer cell lines (IC50 1.1-13.0 µg/mL).
authors.affiliation: Department of Chemistry, Faculty of Science, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia. smariam@upm.edu.my
authors.forename: Siti Mariam Mohd
authors.initials: SM
authors.lastname: Nor
authors.forename: Mohd Aspollah Hj Md
authors.initials: MA
authors.lastname: Sukari
authors.forename: Saripah Salbiah Syed Abdul
authors.initials: SS
authors.lastname: Azziz
authors.forename: Wong Chee
authors.initials: WC
authors.lastname: Fah
authors.forename: Hasimah
authors.initials: H
authors.lastname: Alimon
authors.forename: Siti Fadilah
authors.initials: SF
authors.lastname: Juhan
mesh_terms: D000880:Anthraquinones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects*; D056945:Hep G2 Cells / Q000187:drug effects; D006801:Humans; D061986:MCF-7 Cells / Q000187:drug effects; D015394:Molecular Structure; D013329:Structure-Activity Relationship
chemical_list: D000880:Anthraquinones; C034890:1,4-dihydroxyanthraquinone