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

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.