Synthesis, structural characterization and in vitro antitumor activity of 4-dimethylaminopyridinium (6-chloro-1,1-dioxo-1,4,2-benzodithiazin-3-yl)methanides.
Previously, we have described a novel series of low molecular weight cancer-specific antitumor agents with aminium N-(1,1-dioxo-1,4,2-benzodithiazin-3-yl)arylsulfonamidate structure. In an attempt to determine some of the structural features that account for the cytotoxic activity of such aminium salts, a novel series of 4-dimethylaminopyridinium (1,1-dioxo-1,4,2-benzodithiazin-3-yl)methanides (6-19) has been synthesized by the reactions of 3-methylthio-1,4,2-benzodithiazine1,1-dioxides with 4-DMAP and some active methylene compounds. The in vitro antitumor activity of these compounds has been tested in the National Cancer Institute (NCI), and relationships between structure and antitumor activity are discussed. Among the aminium salts 4-dimethylamino-pyridinium 4-chlorobenzoyl cyano (6-chloro-7-methyl-1,1-dioxo-1,4,2-benzodithiazin-3-yl)methanide (9) was superior to other pyridinium salts in terms of both remarkable activity (log GI50 and logTGI<-8.00) and high selectivity for the lung HOP-92 and melanoma UACC-257 cell lines.
Brzozowski
Zdzislaw
Z
Department of Chemical Technology of Drugs, Medical University of Gdańsk, 80-416 Gdańsk, Poland.
Saczewski
Franciszek
F
Gdaniec
Maria
M
D015761:4-Aminopyridine / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor / Q000379:methods; D006801:Humans; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D015761:4-Aminopyridine; C003885:4-dimethylaminopyridine