Synthesis and cytotoxic activity of lipophilic sulphonamide derivatives of the benzo[b]thiophene 1,1-dioxide.
In the search of new compounds with antineoplastic activity, we have analysed the effect of several structural modifications on the nucleus 6-benzo[b]thiophenesulphonamide 1,1-dioxide on its cytotoxic activity on tumour cells. Lipophilic substituents on the sulphonamide group significantly increased the cytotoxic activity measured using a panel of human tumour cell lines. Only slight variations on cytotoxicity were obtained when the sulphonamide group occupied the position 5 of the system. The most active compound was the N-4-methoxyphenyl derivative 15, which showed GI(50) values of 1-9 nM against HT-29, CCRF-CEM, K-562 and MEL-AC cells and of 200 nM against HTB-54 cells. Free access to the 3-position of the heterocyclic system seems to be required to obtain cytotoxic derivatives. Derivative 15 was also active at the same level of commercial Doxorubicine against cultured normal human lung fibroblasts.
Villar
R
R
Dpto. de Química, Universidad Pública de Navarra, Campus Arrosadía, 31006 Pamplona, Spain.
Encio
I
I
Migliaccio
M
M
Gil
M J
MJ
Martinez-Merino
V
V
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D005347:Fibroblasts / Q000187:drug effects; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D020128:Inhibitory Concentration 50; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis* / Q000494:pharmacology; D013876:Thiophenes / Q000138:chemical synthesis* / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D013449:Sulfonamides; D013876:Thiophenes; C088015:benzothiophene