Evaluation of in vitro biological activity of O-alkylated hydroxamic derivatives of some nonsteroidal anti-inflammatory drugs
Pavelić, Sandra Kraljević × Sedić, Mirela Poznić, Miroslav Rajić, Zrinka Zorc, Branka Pavelić, Kresimir Balzarini, Jan Mintas, Mladen #
Anticancer Research vol:30 issue:10 pages:3987-94
AIM: Several published studies suggest that nonsteroidal anti-inflammatory drugs (NSAIDs) are promising anticancer agents. This study examined the in vitro effect of O-alkylated NSAID hydroxamic acid derivatives 3a-i on cell survival for a panel of human tumour cell lines, their cytotoxicity on normal human fibroblasts and their antiviral activity. MATERIALS AND METHODS: Established methods of cell viability testings, cell cycle analyses and Western blot assays were used. RESULTS: O-Alkylated NSAID hydroxamic acid derivatives exerted poor antiviral activity butreduced the viability of the studied tumour cell lines in a concentration-dependent manner showing low cytotoxic effect on normal fibroblasts. Compounds 3a and 3i were shown to be potent inhibitors of the growth of MIA PaCa-2 cell line. They induced p53-independent S-phase arrest and triggered caspase 3-dependent apoptosis. CONCLUSION: Two novel O-alkylated NSAID hydroxamic acid derivatives may be useful in the treatment of pancreatic cancer and should be further evaluated in vivo.