Synthesis, anti-HIV-1 integrase, and cytotoxic activities of 4-chloro-N-(4-oxopyrimidin-2-yl)-2-mercaptobenzenesulfonamide derivatives.
Several 4-chloro-N-(4-oxopyrimidin-2-yl)-2-mercaptobenzenesulfonamide derivatives 13-28 and 35-44 have been synthesized and tested as potential HIV-1 integrase (IN) inhibitors. Compounds 15-17, 19, 21-28, 36 and 41 inhibited IN with IC(50) values in the range of 3.3-63.0 microM. The compounds 13, 15, 16, 21-24 and 26-28 were further tested at the US National Cancer Institute for their in vitro activity against a panel of 53-57 human tumor cell lines. The compounds 26-28 were inactive, whereas the other compounds exhibited high or reasonable activity (GI(50)<0.01-20.0 microM) against one or more human tumor cell lines.
Brzozowski
Zdzisław
Z
Department of Chemical Technology of Drugs, Medical University of Gdańsk, Al. Gen. Hallera 107, 80-416 Gdańsk, Poland.
Sławiński
Jarosław
J
Saczewski
Franciszek
F
Sanchez
Tino
T
Neamati
Nouri
N
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D019428:HIV Integrase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D015497:HIV-1 / Q000201:enzymology; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D013055:Spectrophotometry, Infrared; D013449:Sulfonamides / Q000138:chemical synthesis* / Q000494:pharmacology*
D000970:Antineoplastic Agents; D019428:HIV Integrase Inhibitors; D013449:Sulfonamides