Synthesis, structural characterization and in vitro antitumor activity of novel 6-chloro-1,1-dioxo-1,4,2-benzodithiazie derivatives.
A series of nonconventional aminium N-(6-chloro-7-R-1,1-dioxo-1,4,2-benzodithiazin-3-yl)arylsulfonamidates 7-15 have been synthesized by the reactions of 6-chloro-7-R-3-methylthio-1,4,2-benzodithiazine 1,1-dioxides with 4-dimethylaminopyridine or Et(3)N and some arylsulfonamides. The free N-(6-chloro-7-methyl-1,1-dioxo-1,4,2-benzodithiazin-3-yl)benzenesulfonamides 16-18 were obtained by treatment of their aminium salts with H(2)SO(4) in boiling acetic acid. The in vitro antitumor activity of the compounds 9, 11-14 and 16-18 has been tested in the antitumor screening of the National Cancer Institute (NCI), and relationships between structure and antitumor activity are discussed. 4-Dimethylaminopyridinium 4-chloro-N-(6-chloro-7-methyl-1,1-dioxo-1,4,2-benzodithiazin-3-yl)benzenesulfonamidate 9 is the prominent of the compounds due to its remarkable activity (log GI(50)<-8.00, log TGI=-5.50) and selectivity for the leukemia SR cell line. For that reason experimental and theoretical analysis of the geometric and electronic properties of 9 was carried out.
Brzozowski
Zdzislaw
Z
Department of Chemical Technology of Drugs, Medical University of Gdańsk, Al. Gen. Hallera 107, 80-416, Gdańsk, Poland.
Saczewski
Franciszek
F
Gdaniec
Maria
M
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000633:toxicity; D045744:Cell Line, Tumor; D006801:Humans; D008956:Models, Chemical; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000494:pharmacology; D013843:Thiazines / Q000138:chemical synthesis / Q000737:chemistry / Q000633:toxicity
D000970:Antineoplastic Agents; D013449:Sulfonamides; D013843:Thiazines