title: Synthesis and anticancer activity of 4-aza-daurinol derivatives.
abstract: Daurinol, a natural aryl naphthalene lactone, has been reported to have antiproliferative activity against various cell lines, and has also been shown to be efficacious in an in vivo xenograft mouse model. In this study, we tried to discover a new scaffold that enables both rapid structure-activity relationship study of daurinol and scalable synthesis of active compounds. 4-Aza-daurinol, a bioisosterism-based scaffold of daurinol, was designed and 17 analogues were synthesized and evaluated against five representative cancer cell lines. Among them, the 2,3-dihydrobenzo[b][1,4]dioxinyl derivative was found to be the most potent and showed similar activity and tendency as daurinol.
authors.affiliation: College of Pharmacy, Gachon University, 191 Hambakmoe-ro, Yeonsu-gu, Incheon, 406-799, South Korea.
authors.forename: Faisal
authors.initials: F
authors.lastname: Hayat
authors.affiliation: College of Pharmacy, Gachon University, 191 Hambakmoe-ro, Yeonsu-gu, Incheon, 406-799, South Korea.
authors.forename: Seung-Hyuk
authors.initials: SH
authors.lastname: Park
authors.affiliation: College of Interdisciplinary & Creative Studies, Konyang University, 121 Daehak-ro, Nonsan-si, Chungchungnam-do, 320-711, South Korea.
authors.forename: Nam-Song
authors.initials: NS
authors.lastname: Choi
authors.affiliation: College of Pharmacy, Hanyang University, 55 Hanyangdaehak-ro, Sangnok-gu, Ansan, Geonggi-do, 426-791, South Korea.
authors.forename: Juyeun
authors.initials: J
authors.lastname: Lee
authors.affiliation: College of Pharmacy, Gachon University, 191 Hambakmoe-ro, Yeonsu-gu, Incheon, 406-799, South Korea. psjnmr@gachon.ac.kr.
authors.forename: Sung Jean
authors.initials: SJ
authors.lastname: Park
authors.affiliation: College of Pharmacy, Gachon University, 191 Hambakmoe-ro, Yeonsu-gu, Incheon, 406-799, South Korea. dyshin@gachon.ac.kr.
authors.forename: Dongyun
authors.initials: D
authors.lastname: Shin
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D052117:Benzodioxoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D009281:Naphthalenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D052117:Benzodioxoles; D009281:Naphthalenes; C571067:daurinol
keywords: Anticancer; Aryltetrahydronaphthalene; Bioisosteric; Daurinol; Structure–activity relationship