engleski

Novel Adamantyl 3-Hydroxypyridin-4-ones: Synthesis and Antiproliferative in vitro Study

3-Hydroxypyridin-4-ones are nowadays widely investigated for their broad spectrum of biological activities (antibacterial, antidiabetes, antiprotozoal, antineurodegenerative and anticancer).[1] Recently, we investigated several N-aryl substituted 3-hydroxy-2- methylpyridin-4-ones as well as their ester adamantyl derivatives for their in vitro antitumor properties on several cancer cell lines.[2] All tested compounds showed antiproliferative activity ranging from moderate to strong on all inspected cell lines with lipophilic adamantane containing derivatives being active at low micromolar IC50 concentrations. Further structure-activity relationship study (SAR) of such and similar pyridinone derivatives as potential anticancer agents is now in progress. In this work, for the purpose of the that study, novel lipophilic adamantyl derivatives of N-aryl substituted 3- hydroxy-2-methylpyridin-4-ones were prepared with the aim of evaluating their in vitro antitumor properties on the panel of cancer cell lines. The compounds were synthesized starting from corresponding pyridinones, which are prepared first in an autoclave, and adamantan-1-ylacetic acid. Antitumor properties of novel compounds will start to elucidate the key elements, primarily the position of adamantyl unit, needed for high antiproliferative activity of observed pyridinone derivatives. In the case of high antiproliferative activities of novel derivatives in vitro testing will include cytotoxicity evaluation and additional testing of the most potent candidates to determine the mechanism of their action more precisely. Acknowledgements: This research is financially supported by Croatian Science Foundation (project IP 2014-09- 7899)

3-hydroxypyridin-4-ones, adamantan-1-ylacetic acid, antitumor, SAR

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