Structure activity relationship analysis of antiproliferative cyclic C5-curcuminoids without DNA binding: Design, synthesis, lipophilicity and biological activity

Publication date: 15 April 2020Source: Journal of Molecular Structure, Volume 1206Author(s): Imre Huber, Zsuzsanna Rozmer, Zoltán Gyöngyi, Ferenc Budán, Péter Horváth, Eszter Kiss, Pál PerjésiAbstractThe chemical susceptibility of the β-diketone linker between the two aromatic rings in the structure of curcumin to hydrolysis and metabolism has made it crucial to investigate structurally modified analogs of curcumin without such shortcomings. The synthesis of twenty cyclic C5-curcuminoids is described in this study in order to gain more insight into their anticancer structure-activity relationship (SAR). The design of their synthesis included four different cyclanones and five substituted aromatic aldehydes to form four, five-membered subgroups. These model compounds were evaluated in vitro for antiproliferative activity in an XTT cell viability assay against MCF-7 human non-invasive breast adenocarcinoma cancer cells and Jurkat human T lymphocyte leukemia cells in five different concentrations (10 nM, 100 nM, 1 μM, 10 μM and 20 μM). The majority of the compounds investigated have shown remarkable cytotoxicity with IC50 values in the range of 120 nM and 2 μM with very high relative toxicity values to curcumin. The SAR conclusions are drawn and summarized. A method was developed and applied in a TLC based experimental logP measurement, which is new for such C5-curcuminoids. The logP data and structural modifications have shown a strong correlation. The corre...
Source: Journal of Molecular Structure - Category: Molecular Biology Source Type: research