Synthesis and in vitro antitumor activity of novel series 2-benzylthio-4-chlorobenzenesulfonamide derivatives.
Three series of novel 2-benzylthio-4-chloro-5-R1-benzenesulfonamides bearing the N-(benzoxazol-2-yl) (10-19), N-(benzothiazol-2-yl) (20-21) or N-(1,3-dihydro-2H-benzimidazol-2-ylidene) (22-25) moiety were synthesized by reacting N-(2-benzylthio-4-chloro-5-R1-benzenesulfonyl)cyanamide potassium salts (5-9) with 2-aminophenols, 2-aminothiophenol and o-phenylenediamines, respectively. Compounds with carbamoyl substituent at position 5 (14-16, 21 and 25, R1=CONH2) were further dehydrated to the corresponding nitriles (26-30, R1=CN). The in vitro antitumor activity of the compounds obtained was determined at the National Cancer Institute (NCI), and the structure-activity relationships were discussed. N-(2-benzoxazolyl)-2-benzylthio-4-chloro-5-(4-fluorophenylcarbamoyl)benzenesulfonamide (18) is the prominent of the compounds due to its remarkable activity and selectivity toward non-small cell lung cancer (NCI-H522) and melanoma (SK-MEL-2) cell lines (GI50=0.1 microM, TGI=0.5-0.6 microM).
Sławiński
J
J
Department of Chemical Technology of Drugs, Medical University of Gdańsk, Al. Gen. J. Hallera 107, 80-416 Gdańsk, Poland. jaroslaw@amg.gda.pl
Brzozowski
Z
Z
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001593:Benzyl Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D015394:Molecular Structure; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000096926:Benzenesulfonamides
D000970:Antineoplastic Agents; D001593:Benzyl Compounds; D013449:Sulfonamides; C516489:2-benzylthio-4-chlorobenzenesulfonamide; D000096926:Benzenesulfonamides