engleski

In vitro antiproliferative study of novel adamantyl pyridin-4-ones

The preparation of several N-aryl substituted (phenyl, p-methylphenyl, p-methoxyphenyl, p- nitrophenyl, p-aminophenyl, p-hydroxyphenyl) 3- hydroxy-2-methylpyridin-4-ones as well as their adamantyl derivatives is described and their in vitro antitumor properties investigated. The compounds were synthesized in good yields using efficient synthetic routes and methods. Prepared derivatives were evaluated in an antiproliferative in vitro study on 4 cancer cell lines, namely HCT 116 (colon carcinoma), H 460 (lung carcinoma), MCF-7 (breast carcinoma) and K562 (chronic myelogenous leukemia, CML). All tested compounds showed antiproliferative activity ranging from moderate to strong on all inspected cell lines with 4 adamantane containing derivatives being active and selective at low micromolar IC50 concentrations on HCT 116, H 460 and MCF-7. LDH cytotoxicity assay revealed that the cytotoxic effects occur after 48 hours of exposure. It was shown that there was no change in caspase activity in the treated cells but there were changes in the cell cycle. All treated samples showed reduced number of cells in the S phase, with increased G0/G1 (4b, 5a, 5b) and G2/M (4a) phase.

N-aryl 3-hydroxy-2-methylpyridin-4-ones, Adamantyl, Lipophilicity, Antiproliferative in vitro study

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