Synthesis, molecular structure, and in vitro antitumor activity of new 4-chloro-2-mercaptobenzenesulfonamide derivatives.
The reaction of 3-amino-2-(2-alkylthio-4-chlorobenzenesulfonyl)guanidines 2a-j with 1,2-dicarbonyl compounds are described. Depending on structure of 1,2-dicarbonyl reagent novel 2-alkylthio-5-chloro-N-(1,2,4-triazin-3-yl)benzenesulfonamides 3-15, 1-(2-alkylthio-4-chlorobenzenesulfonyl)-3-(2-oxobutane-3-ylidenoimino)guanidines 16-18 and 2-alkylthio-4-chloro-N-(1,2-dihydroxycyclobuta[e]1,2,4-triazin-3-yl)benzenesulfonamides 19-21 are obtained. The structures of these compounds were confirmed on the basis of elemental analysis, spectral data and X-ray analysis. The compounds 4, 5, 7, 9, 10, 12-15, 17, 18 and 20 were screened at the National Cancer Institute (NCI) for their in vitro activities against a panel of 56 tumor cell lines and relationship between structure and antitumor activity are discussed. The compounds 10, 12, 17 and 20 were inactive, whereas the other compounds exhibited reasonable activity against one or more human tumor cell lines. The prominent compound 18 showed significant activity against cell lines of colon cancer (HCT-116), renal cancer (786-0) and melanoma (M14) (GI50 in the range 0.33-1.08 microM) as well as good selectivity toward non-small cell lung cancer (HOP-62) cells (GI50 = 0.05 microM, TGI = 0.38 microM and LC50 = 4.83 microM).
Sławiński
Jarosław
J
Department of Chemical Technology of Drugs, Medical University of Gdańsk, Al. Gen. J. Hallera 107, 80-416 Gdańsk, Poland. jaroslaw@amg.gda.pl
Gdaniec
Maria
M
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D006801:Humans; D006860:Hydrogen Bonding; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000096926:Benzenesulfonamides
D000970:Antineoplastic Agents; D013449:Sulfonamides; C502762:4-chloro-2-mercaptobenzenesulfonamide; D000096926:Benzenesulfonamides