Synthesis, antitumor and anti-HIV activities of benzodithiazine-dioxides.
Several 8-chloro-7-R1-6-R2-3-R3-imidazo[1,2-b][1,4,2]benzodithiazine 5,5-dioxide derivatives (9-11, 16-19, and 21-24) have been synthesized as potential antitumor or anti-HIV agents. The in vitro antitumor and anti-HIV-1 activities of the compounds were determined in a panel of cell lines. The benzodithiazine-dioxide 10 showed 50% growth inhibitory activity in low micromolar against most cells. It was particularly effective in leukemia, lung, melanoma, ovarian, and renal cancer cells with GI50 values of 1-2 microM. Interestingly, benzodithiazine-dioxide 16 showed remarkable anti-HIV-1 activity with 50% effective concentration EC50 value of 0.94 microM and no significant cytotoxicity at 200.0 microM.
Brzozowski
Zdziasław
Z
Department of Chemical Technology of Drugs, Medical University of Gdańsk, 80-416 Gdańsk, Poland.
Saczewski
Franciszek
F
Neamati
Nouri
N
D000812:Anhydrides / Q000737:chemistry; D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002713:Chlorine / Q000737:chemistry; D004353:Drug Evaluation, Preclinical; D004952:Esters / Q000737:chemistry; D015497:HIV-1 / Q000187:drug effects; D006801:Humans; D007093:Imidazoles / Q000737:chemistry; D008745:Methylation; D015394:Molecular Structure; D010100:Oxygen / Q000737:chemistry*; D013329:Structure-Activity Relationship; D013843:Thiazines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*
D000812:Anhydrides; D019380:Anti-HIV Agents; D000970:Antineoplastic Agents; D004952:Esters; D007093:Imidazoles; D013843:Thiazines; D002713:Chlorine; C029899:imidazole; D010100:Oxygen