start-ver=1.4
cd-journal=joma
no-vol=16
cd-vols=
no-issue=2
article-no=
start-page=922
end-page=940
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2008
dt-pub=20080115
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Antitumor studies. Part 4: Design, synthesis, antitumor activity, and molecular docking study of novel 2-substituted 2-deoxoflavin-5-oxides, 2-deoxoalloxazine-5-oxides, and their 5-deaza analogs
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Various novel 10-alkyl-2-deoxo-2-methylthioflavin-5-oxides and their 2-alkylamino derivatives were prepared by facile nitrosative cyclization of 6-(N-alkylanilino)-2-methylthiopyrimidin-4(3H)-ones followed by nucleophilic replacement of the 2-methylthio moiety by different amines, and acidic hydrolysis of the 2-methylthio moiety afforded the corresponding flavin derivatives. 2-Deoxo-2-methylthio-5-deazaalloxazines and 2-deoxo-2-methylthioalloxazine-5-oxides were also prepared by Vilsmeier reaction and by nitrosation of 6-anilino-2-methylthiopyrimidin-4(3H)-ones, respectively. Then, they were subjected to nucleophilic replacement with appropriate amines to produce the corresponding 2-alkylamino derivatives. Regiospecific N-3-alkylation of 2-deoxo-2-methylthioalloxazine-5-oxides was carried out with various alkylating agents in the usual way, The antitumor activities against CCRF-HSB-2 and KB tumor cells have been investigated in vitro, and many compounds showed promising antitumor activities. Furthermore, AutoDock molecular docking into PTK (PDB: 1t46) has been done for lead optimization of the aforementioned compounds as potential PTK inhibitors.
en-copyright=
kn-copyright=

en-aut-name=AliHamed I.
en-aut-sei=Ali
en-aut-mei=Hamed I.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=AshidaNoriyuki
en-aut-sei=Ashida
en-aut-mei=Noriyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=NagamatsuTomohisa
en-aut-sei=Nagamatsu
en-aut-mei=Tomohisa
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

affil-num=1
en-affil=
kn-affil=Department of Drug Discovery and Development, Division of Pharmaceutical Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University

affil-num=2
en-affil=
kn-affil=Biology Laboratory, Research and Development Division, Yamasa Shoyu Co.

affil-num=3
en-affil=
kn-affil=Department of Drug Discovery and Development, Division of Pharmaceutical Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
en-keyword=antitumor activity
kn-keyword=antitumor activity
en-keyword=flavin-5-oxide
kn-keyword=flavin-5-oxide
en-keyword=alloxazine-5-oxide
kn-keyword=alloxazine-5-oxide
en-keyword=AutoDock
kn-keyword=AutoDock
END