Evaluation of in vitro biological activity of O-alkylated hydroxamic derivatives of some nonsteroidal anti-inflammatory drugs.

Abstract

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.

• Authors: Sandra Kraljević Pavelić, Mirela Sedić, Miroslav Poznić, Zrinka Rajić, Branka Zorc, Kresimir Pavelić, Jan Balzarini, Mladen Mintas
• Journal: Anticancer research (Anticancer Res) Vol. 30 Issue 10 Pg. 3987-94 (Oct 2010) ISSN: 1791-7530 [Electronic] Greece
• PMID: 21036712 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Inflammatory Agents, Non-Steroidal
• Antineoplastic Agents
• Antiviral Agents
• Hydroxamic Acids

Topics

• Animals
• Anti-Inflammatory Agents, Non-Steroidal (pharmacology)
• Antineoplastic Agents (pharmacology)
• Antiviral Agents (pharmacology)
• Apoptosis (drug effects)
• Cell Cycle (drug effects)
• Cell Line, Tumor
• Cell Survival (drug effects)
• Drug Screening Assays, Antitumor
• HeLa Cells
• Humans
• Hydroxamic Acids (pharmacology)
• Leukemia L1210 (drug therapy)
• Structure-Activity Relationship