title: Synthesis, antiviral, and anti-HIV-1 integrase activities of 3-aroyl-1,1-dioxo-1,4,2-benzodithiazines.
abstract: 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.
authors.affiliation: Department of Chemical Technology of Drugs, Medical University of Gdansk, Al. Gen. Hallera 107, 80-416 Gdansk, Poland.
authors.forename: Zdzislaw
authors.initials: Z
authors.lastname: Brzozowski
authors.forename: Franciszek
authors.initials: F
authors.lastname: Saczewski
authors.forename: Tino
authors.initials: T
authors.lastname: Sanchez
authors.forename: Chih-Ling
authors.initials: CL
authors.lastname: Kuo
authors.forename: Maria
authors.initials: M
authors.lastname: Gdaniec
authors.forename: Nouri
authors.initials: N
authors.lastname: Neamati
mesh_terms: 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
chemical_list: D019380:Anti-HIV Agents; D001554:Benzene; D019427:HIV Integrase; D019428:HIV Integrase Inhibitors; D013449:Sulfonamides; D013843:Thiazines; D000096926:Benzenesulfonamides