Synthesis of a new series of 4-chloro-2-mercapto-5-methylbenzenesulfonamide derivatives with potential antitumor activity.
The syntheses of S-(5-chloro-4-methyl-2-sulfamoylphenyl)alkanethio (or benzothio)hydrazonates (3a-3o) and potassium S-(5-chloro-2-cyanoamidatesulfonyl-4-methylphenyl)alkanethio (or benzothio)hydrazonates (4-10) are described. The compounds 3e, 3i-3o, 7 and 8 were screened at the National Cancer Institute (NCI) for their activities against a panel of 59 tumor cell lines and relationships between structure and antitumor activity in vitro are discussed. The compounds 3e, 3j, 3l-3o and 7 exhibited reasonable activity against numerous human tumor cell lines. The prominent compound 3l showed significant activity against some cell lines of leukemia (SR), melanoma (SK-MEL-5), CNS cancer (SF-539), ovarian cancer (OVCAR-3, OVCAR-4) and breast cancer (MDA-MB-231/ACTT) (GI50 values in the range 0.3-0.9 microM). Furthermore, compound 8 exhibited the high selectivity against renal cancer (A498) cells (GI50 < 0.01 microM, TGI = 2.3 microM and LC50 = 35.7 microM).
Department of Chemical Technology of Drugs, Medical University of Gdańsk, Al. Gen. J. Hallera 107, 80-416 Gdansk, Poland. jaroslaw@amg.gda.pl
Jarosław
J
Sławiński
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D013438:Sulfhydryl Compounds / Q000138:chemical synthesis* / Q000494:pharmacology*; D013449:Sulfonamides / Q000138:chemical synthesis* / Q000494:pharmacology*; D000096926:Benzenesulfonamides
D000970:Antineoplastic Agents; D013438:Sulfhydryl Compounds; D013449:Sulfonamides; C492566:4-chloro-2-mercapto-5-methylbenzenesulfonamide; D000096926:Benzenesulfonamides