《Structure activity relationship analysis of antiproliferative cyclic C5-curcuminoids without DNA binding: Design, synthesis, lipophilicity and biological activity》 was published in Journal of Molecular Structure in 2020. These research results belong to Huber, Imre; Rozmer, Zsuzsanna; Gyongyi, Zoltan; Budan, Ferenc; Horvath, Peter; Kiss, Eszter; Perjesi, Pal. Product Details of 1445-73-4 The article mentions the following:
The chem. 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, I (R = NO2, Cl, H, MeO, NMe2, X = CHMe, NH, NMe, CHOH), 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, 1μM, 10μM and 20μM). The majority of the compounds investigated have shown remarkable cytotoxicity with IC50 values in the range of 120 nM and 2μM 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 exptl. logP measurement, which is new for such C5-curcuminoids. The logP data and structural modifications have shown a strong correlation. The correlation of these exptl. logP and the corresponding IC50 values of the model-compounds were calculated according to the Pearson and Kendall correlation coefficient and showed weak concordance. The physicochem. behaviors of the majority of these compounds are in good accordance with Lipinski’s rule. The most promising compound is I (R = NO2, X = NH), which is the most active (IC50 = 0.12-0.32μM) and most potent (80 times of curcumin) compound with the lowest lipophilicity (exptl. logP = 3.22), which is important also from a pharmacokinetic point of view. The anal. of exptl. logP and computed ClogP values have revealed good agreement. These cyclic C5-curcuminoids in contrast to curcumin do not bind to natural DNA based on their CD spectra. The results came from multiple reactions, including the reaction of 1-Methyl-4-piperidone(cas: 1445-73-4Product Details of 1445-73-4)
1-Methyl-4-piperidone(cas: 1445-73-4) is a member of piperidine. Piperidine is a key saturated heterocyclic scaffold found in several of the top-selling small molecule pharmaceuticals and natural alkaloids, with a diverse range of biological activities. Hence, continuous efforts have been made to develop convenient methods to prepare piperidine derivatives.Product Details of 1445-73-4
Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem