A novel cluster of C5-curcuminoids: design, synthesis, in vitro antiproliferative activity and DNA binding of bis(arylidene)-4-cyclanone derivatives based on 4-hydroxycyclohexanone scaffold

Imre Huber, István Zupkó, András Gyovai, Péter Horváth, Eszter Kiss, Gergely Gulyás-Fekete, János Schmidt, Pál Perjési

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Abstract

A new series (6) of C5-curcuminoid derivatives (2E,6E-2,6-dibenzylidene-4-hydroxycyclohexanones) is described here with their evaluation for in vitro antiproliferative activities. Evaluation of 31 compounds against human A2780 (ovarian), C33A (cervix) and MDA-MB-231 (breast) cancer cell lines was performed to obtain structure activity relation data. The best performer was (2E,6E)-2,6-bis(3′-nitrobenzylidene)-4-hydroxycyclohexanone (6h) with IC50 values of 0.68 μM (A2780), 0.69 μM (C33A) and 0.92 μM (MDA-MB-231) compared to cisplatin with 1.30 μM, 3.69 μM and 19.13 μM, respectively. According to calculated physicochemical properties some members in series 6, namely (2E,6E)-2,6-bis[(4′-pyridinyl)methylene]-4-hydroxycyclohexanone (6p) [IC50 = 0.76 μM (A2780), 2.69 μM (C33A), 1.28 μM (MDA-MB-231)] seem to have improved bioavailability compared to curcumin. Selected members of series 6 were involved in circular dichroism spectroscopic measurements in order to determine their interaction with natural DNA. Based on these data, we conclude that these derivatives do not bind to DNA in vitro. A proposal is summarized based on mass spectrometric assessment for fingerprint analysis in biological research of such C5-curcuminoids.

Original languageEnglish
JournalResearch on Chemical Intermediates
DOIs
Publication statusPublished - jan. 1 2019

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ASJC Scopus subject areas

  • Chemistry(all)

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