Efficient Consecutive Synthesis of Fluorinated Isoflavone Analogs, X-Ray Structures, Hirshfeld Analysis, and Anticancer Activity Assessment

The synthesis of 7-<i>O</i>-carboxymethyl-4′-fluoroisoflavone <b>4</b> and 7-<i>O</i>-carboxymethyl-4′-fluoro-2-trifluormethylisoflavone <b>7</b> involved the cyclization of 2,4-dihydroxy-4′-fluorodeoxybenzoin <b>1</b>, followed by 7-<i&...

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Bibliographic Details
Main Authors: Mohammed Salah Ayoup, Malak Daqa, Yousef Salama, Rand Hazzam, Mohammed B. Hawsawi, Saied M. Soliman, Nawaf Al-Maharik
Format: Article
Language:English
Published: MDPI AG 2025-02-01
Series:Molecules
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Online Access:https://www.mdpi.com/1420-3049/30/4/795
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Summary:The synthesis of 7-<i>O</i>-carboxymethyl-4′-fluoroisoflavone <b>4</b> and 7-<i>O</i>-carboxymethyl-4′-fluoro-2-trifluormethylisoflavone <b>7</b> involved the cyclization of 2,4-dihydroxy-4′-fluorodeoxybenzoin <b>1</b>, followed by 7-<i>O</i>-alkylation with methyl bromoacetate and subsequent acid-catalyzed hydrolysis. The structures of the novel compounds were validated using a range of techniques, including XRD crystallography (<sup>1</sup>H, <sup>19</sup>F, <sup>13</sup>C)-NMR, and IR. Only interhalogen contacts were detected in <b>5</b>, while they were completely lacking in <b>2</b> and <b>4</b>, owing to the presence of crystalline ethanol in the crystal structure. The %F…F in <b>5</b> was 12.2% based on Hirshfeld calculations. The aromatic π-π stacking interactions were important only in <b>2</b> and <b>4</b> but not observed in <b>5</b>. Isoflavones <b>4</b>, <b>5</b>, and <b>7</b> displayed anticancer activity against MCF-7 cancer cells, with IC<sub>50</sub> values of 13.66, 15.43, and 11.73 µM, respectively.
ISSN:1420-3049