title: Antitumor studies. part 3: design, synthesis, antitumor activity, and molecular docking study of novel 2-methylthio-, 2-amino-, and 2-(N-substituted amino)-10-alkyl-2-deoxo-5-deazaflavins.
abstract: Various novel 10-alkyl-2-deoxo-2-methylthio-5-deazaflavins have been synthesized by reaction of 6-(N-alkylanilino)-2-methylthiopyrimidin-4(3H)-ones with Vilsmeier reagent. The similar 2-(N-substituted amino) derivatives were prepared by nucleophilic replacement reaction of the 2-methylthio moiety by appropriate amines. The 2-oxo derivatives (i.e., 5-deazaflavins) were obtained by acidic hydrolysis of the 2-methylthio derivatives. The antitumor activities against CCRF-HSB-2 and KB cells and the antiviral activities against HSV-1 and HSV-2 have been investigated in vitro, and many compounds showed promising antitumor activities. Furthermore, AutoDock molecular docking into PTK has been done for lead optimization of these compounds as potential PTK inhibitors. Whereas, the designed 2-deoxo-5-deazaflavins connected with amino acids at the 2-position exhibited the good binding affinities into PTK with more hydrogen bonds.
authors.affiliation: Department of Drug Discovery and Development, 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: Noriyuki
authors.initials: N
authors.lastname: Ashida
authors.forename: Tomohisa
authors.initials: T
authors.lastname: Nagamatsu
mesh_terms: D000596:Amino Acids / Q000737:chemistry; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D000998:Antiviral Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D001665:Binding Sites; D045744:Cell Line, Tumor / Q000187:drug effects; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D005415:Flavins / Q000138:chemical synthesis / Q000494:pharmacology*; D006801:Humans; D006860:Hydrogen Bonding; D020128:Inhibitory Concentration 50; D013056:Spectrophotometry, Ultraviolet; D013329:Structure-Activity Relationship; D013997:Time Factors
chemical_list: D000596:Amino Acids; D000970:Antineoplastic Agents; D000998:Antiviral Agents; D005415:Flavins