Synthesis, antiviral, and anti-HIV-1 integrase activities of 3-aroyl-1,1-dioxo-1,4,2-benzodithiazines.
HIV-1 integrase (IN) is an essential enzyme for effective viral replication and is an attractive target for selective blockade of viral infection. Previously, we identified a series of sulfones, sulfonamides, and mercaptosalicylhydrazides (MBSAs) as IN inhibitors with antiviral activities in cell-based assays. In an effort to optimize a series of our active site directed lead compounds, we designed and synthesized novel benzodithiazines starting from MBSAs. In contrast to all reported IN inhibitors benzodithiazines are essentially nontoxic. Significant antiviral potency was only observed at concentration exceedingly higher than that required to inhibit purified IN.
Brzozowski
Zdzislaw
Z
Department of Chemical Technology of Drugs, Medical University of Gdansk, Al. Gen. Hallera 107, 80-416 Gdansk, Poland.
Saczewski
Franciszek
F
Sanchez
Tino
T
Kuo
Chih-Ling
CL
Gdaniec
Maria
M
Neamati
Nouri
N
D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001554:Benzene / Q000737:chemistry; D002460:Cell Line; D018360:Crystallography, X-Ray; D019427:HIV Integrase / Q000378:metabolism*; D019428:HIV Integrase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D015497:HIV-1 / Q000187:drug effects / Q000201:enzymology; D006801:Humans; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D013449:Sulfonamides / Q000138:chemical synthesis / Q000737:chemistry; D013843:Thiazines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D000096926:Benzenesulfonamides
D019380:Anti-HIV Agents; D001554:Benzene; D019427:HIV Integrase; D019428:HIV Integrase Inhibitors; D013449:Sulfonamides; D013843:Thiazines; D000096926:Benzenesulfonamides