title: Antitumor studies. Part 1: design, synthesis, antitumor activity, and AutoDock study of 2-deoxo-2-phenyl-5-deazaflavins and 2-deoxo-2-phenylflavin-5-oxides as a new class of antitumor agents.
abstract: Novel 2-deoxo-2-phenyl-5-deazaflavins and 2-deoxo-2-phenylflavin-5-oxides were prepared as a new class of antitumor agents and showed significant antitumor activities against NCI-H 460, HCT 116, A 431, CCRF-HSB-2, andKB cell lines. In vivo investigation, 2-deoxo-10-methyl-2-phenyl-5-deazaflavin exhibited the effective antitumor activity against A 431 human adenocarcinoma cells transplanted subcutaneously into nude mouse. Furthermore, AutoDock study has been done by binding of the flavin analogs into PTK pp60(c-src), where a good correlation between their IC(50) and AutoDock binding free energy was exhibited. In particular, 2-deoxo-2-phenylflavin-5-oxides exhibited the highest potential binding affinity within the binding pocket of PTK.
authors.affiliation: Division of Pharmaceutical Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University 1-1-1, Tsushima-naka, Okayama 700-8530, Japan.
authors.forename: Hamed I
authors.initials: HI
authors.lastname: Ali
authors.forename: Keiichiro
authors.initials: K
authors.lastname: Tomita
authors.forename: Eiichi
authors.initials: E
authors.lastname: Akaho
authors.forename: Hiroto
authors.initials: H
authors.lastname: Kambara
authors.forename: Shinji
authors.initials: S
authors.lastname: Miura
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Hayakawa
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Ashida
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Kawashima
authors.forename: Takehiro
authors.initials: T
authors.lastname: Yamagishi
authors.forename: Hisao
authors.initials: H
authors.lastname: Ikeya
authors.forename: Fumio
authors.initials: F
authors.lastname: Yoneda
authors.forename: Tomohisa
authors.initials: T
authors.lastname: Nagamatsu
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000145:classification / Q000494:pharmacology; D001665:Binding Sites; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003198:Computer Simulation; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D005415:Flavins / Q000138:chemical synthesis* / Q000145:classification* / Q000494:pharmacology*; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D015394:Molecular Structure; D010087:Oxides / Q000138:chemical synthesis* / Q000145:classification* / Q000494:pharmacology*; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013997:Time Factors
chemical_list: C517087:2-deoxo-2-phenylflavin-5-oxide; D000970:Antineoplastic Agents; D005415:Flavins; D008024:Ligands; D010087:Oxides; C019319:5-deazaflavin