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&...
Saved in:
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2025-02-01
|
| Series: | Molecules |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1420-3049/30/4/795 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850081844875231232 |
|---|---|
| author | Mohammed Salah Ayoup Malak Daqa Yousef Salama Rand Hazzam Mohammed B. Hawsawi Saied M. Soliman Nawaf Al-Maharik |
| author_facet | Mohammed Salah Ayoup Malak Daqa Yousef Salama Rand Hazzam Mohammed B. Hawsawi Saied M. Soliman Nawaf Al-Maharik |
| author_sort | Mohammed Salah Ayoup |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-418879adb36d4b0e8d0d4b81fe0752d7 |
| institution | DOAJ |
| issn | 1420-3049 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj-art-418879adb36d4b0e8d0d4b81fe0752d72025-08-20T02:44:39ZengMDPI AGMolecules1420-30492025-02-0130479510.3390/molecules30040795Efficient Consecutive Synthesis of Fluorinated Isoflavone Analogs, X-Ray Structures, Hirshfeld Analysis, and Anticancer Activity AssessmentMohammed Salah Ayoup0Malak Daqa1Yousef Salama2Rand Hazzam3Mohammed B. Hawsawi4Saied M. Soliman5Nawaf Al-Maharik6Department of Chemistry, College of Science, King Faisal University, Al-Ahsa 31982, Saudi ArabiaDepartment of Chemistry, Science College, An-Najah National University, P.O. Box 7, Nablus 00970, PalestineAn-Najah Center for Cancer and Stem Cell Research, Faculty of Medicine and Health Sciences, An-Najah National University, P.O. Box 7, Nablus 00970, PalestineDepartment of Chemistry, Science College, An-Najah National University, P.O. Box 7, Nablus 00970, PalestineDepartment of Chemistry, Faculty of Science, Umm Al-Qura University, Makkah 21955, Saudi ArabiaDepartment of Chemistry, Faculty of Science, Alexandria University, Alexandria 21321, EgyptDepartment of Chemistry, Science College, An-Najah National University, P.O. Box 7, Nablus 00970, PalestineThe 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.https://www.mdpi.com/1420-3049/30/4/7954′-fluoroisflavones7-<i>O</i>-carboxmethyl-4′-fluoroisoflavoneXRD crystallographyanticancerMCF7 cancer cells |
| spellingShingle | Mohammed Salah Ayoup Malak Daqa Yousef Salama Rand Hazzam Mohammed B. Hawsawi Saied M. Soliman Nawaf Al-Maharik Efficient Consecutive Synthesis of Fluorinated Isoflavone Analogs, X-Ray Structures, Hirshfeld Analysis, and Anticancer Activity Assessment Molecules 4′-fluoroisflavones 7-<i>O</i>-carboxmethyl-4′-fluoroisoflavone XRD crystallography anticancer MCF7 cancer cells |
| title | Efficient Consecutive Synthesis of Fluorinated Isoflavone Analogs, X-Ray Structures, Hirshfeld Analysis, and Anticancer Activity Assessment |
| title_full | Efficient Consecutive Synthesis of Fluorinated Isoflavone Analogs, X-Ray Structures, Hirshfeld Analysis, and Anticancer Activity Assessment |
| title_fullStr | Efficient Consecutive Synthesis of Fluorinated Isoflavone Analogs, X-Ray Structures, Hirshfeld Analysis, and Anticancer Activity Assessment |
| title_full_unstemmed | Efficient Consecutive Synthesis of Fluorinated Isoflavone Analogs, X-Ray Structures, Hirshfeld Analysis, and Anticancer Activity Assessment |
| title_short | Efficient Consecutive Synthesis of Fluorinated Isoflavone Analogs, X-Ray Structures, Hirshfeld Analysis, and Anticancer Activity Assessment |
| title_sort | efficient consecutive synthesis of fluorinated isoflavone analogs x ray structures hirshfeld analysis and anticancer activity assessment |
| topic | 4′-fluoroisflavones 7-<i>O</i>-carboxmethyl-4′-fluoroisoflavone XRD crystallography anticancer MCF7 cancer cells |
| url | https://www.mdpi.com/1420-3049/30/4/795 |
| work_keys_str_mv | AT mohammedsalahayoup efficientconsecutivesynthesisoffluorinatedisoflavoneanalogsxraystructureshirshfeldanalysisandanticanceractivityassessment AT malakdaqa efficientconsecutivesynthesisoffluorinatedisoflavoneanalogsxraystructureshirshfeldanalysisandanticanceractivityassessment AT yousefsalama efficientconsecutivesynthesisoffluorinatedisoflavoneanalogsxraystructureshirshfeldanalysisandanticanceractivityassessment AT randhazzam efficientconsecutivesynthesisoffluorinatedisoflavoneanalogsxraystructureshirshfeldanalysisandanticanceractivityassessment AT mohammedbhawsawi efficientconsecutivesynthesisoffluorinatedisoflavoneanalogsxraystructureshirshfeldanalysisandanticanceractivityassessment AT saiedmsoliman efficientconsecutivesynthesisoffluorinatedisoflavoneanalogsxraystructureshirshfeldanalysisandanticanceractivityassessment AT nawafalmaharik efficientconsecutivesynthesisoffluorinatedisoflavoneanalogsxraystructureshirshfeldanalysisandanticanceractivityassessment |