Exploring the Binding of Natural Compounds to Cancer-Related G-Quadruplex Structures: From 9,10-Dihydrophenanthrenes to Their Dimeric and Glucoside Derivatives
In-depth studies on the interaction of natural compounds with cancer-related G-quadruplex structures have been undertaken only recently, despite their high potential as anticancer agents, especially due to their well-known and various bioactivities. In this frame, aiming at expanding the repertoire...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-04-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/9/7765 |
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| author | Chiara Platella Andrea Criscuolo Claudia Riccardi Rosa Gaglione Angela Arciello Domenica Musumeci Marina DellaGreca Daniela Montesarchio |
| author_facet | Chiara Platella Andrea Criscuolo Claudia Riccardi Rosa Gaglione Angela Arciello Domenica Musumeci Marina DellaGreca Daniela Montesarchio |
| author_sort | Chiara Platella |
| collection | DOAJ |
| description | In-depth studies on the interaction of natural compounds with cancer-related G-quadruplex structures have been undertaken only recently, despite their high potential as anticancer agents, especially due to their well-known and various bioactivities. In this frame, aiming at expanding the repertoire of natural compounds able to selectively recognize G-quadruplexes, and particularly focusing on phenanthrenoids, a mini-library including dimeric (<b>1</b>–<b>3</b>) and glucoside (<b>4</b>–<b>5</b>) analogues of 9,10-dihydrophenanthrenes, a related tetrahydropyrene glucoside (<b>6</b>) along with 9,10-dihydrophenanthrene <b>7</b> were investigated here by several biophysical techniques and molecular docking. Compounds <b>3</b> and <b>6</b> emerged as the most selective G-quadruplex ligands within the investigated series. These compounds proved to mainly target the grooves/flanking residues of the hybrid telomeric and parallel oncogenic G-quadruplex models exploiting hydrophobic, hydrogen bond and π-π interactions, without perturbing the main folds of the G-quadruplex structures. Notably, a binding preference was found for both ligands towards the hybrid telomeric G-quadruplex. Moreover, compounds <b>3</b> and <b>6</b> proved to be active on different human cancer cells in the low micromolar range. Overall, these compounds emerged as useful ligands able to target G-quadruplex structures, which are of interest as promising starting scaffolds for the design of analogues endowed with high and selective anticancer activity. |
| first_indexed | 2024-03-11T04:18:00Z |
| format | Article |
| id | doaj.art-4257a3da53c844359929cfacd7faa77d |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T04:18:00Z |
| publishDate | 2023-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-4257a3da53c844359929cfacd7faa77d2023-11-17T23:00:19ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-04-01249776510.3390/ijms24097765Exploring the Binding of Natural Compounds to Cancer-Related G-Quadruplex Structures: From 9,10-Dihydrophenanthrenes to Their Dimeric and Glucoside DerivativesChiara Platella0Andrea Criscuolo1Claudia Riccardi2Rosa Gaglione3Angela Arciello4Domenica Musumeci5Marina DellaGreca6Daniela Montesarchio7Department of Chemical Sciences, University of Naples Federico II, Via Cintia 21, 80126 Naples, ItalyDepartment of Chemical Sciences, University of Naples Federico II, Via Cintia 21, 80126 Naples, ItalyDepartment of Chemical Sciences, University of Naples Federico II, Via Cintia 21, 80126 Naples, ItalyDepartment of Chemical Sciences, University of Naples Federico II, Via Cintia 21, 80126 Naples, ItalyDepartment of Chemical Sciences, University of Naples Federico II, Via Cintia 21, 80126 Naples, ItalyDepartment of Chemical Sciences, University of Naples Federico II, Via Cintia 21, 80126 Naples, ItalyDepartment of Chemical Sciences, University of Naples Federico II, Via Cintia 21, 80126 Naples, ItalyDepartment of Chemical Sciences, University of Naples Federico II, Via Cintia 21, 80126 Naples, ItalyIn-depth studies on the interaction of natural compounds with cancer-related G-quadruplex structures have been undertaken only recently, despite their high potential as anticancer agents, especially due to their well-known and various bioactivities. In this frame, aiming at expanding the repertoire of natural compounds able to selectively recognize G-quadruplexes, and particularly focusing on phenanthrenoids, a mini-library including dimeric (<b>1</b>–<b>3</b>) and glucoside (<b>4</b>–<b>5</b>) analogues of 9,10-dihydrophenanthrenes, a related tetrahydropyrene glucoside (<b>6</b>) along with 9,10-dihydrophenanthrene <b>7</b> were investigated here by several biophysical techniques and molecular docking. Compounds <b>3</b> and <b>6</b> emerged as the most selective G-quadruplex ligands within the investigated series. These compounds proved to mainly target the grooves/flanking residues of the hybrid telomeric and parallel oncogenic G-quadruplex models exploiting hydrophobic, hydrogen bond and π-π interactions, without perturbing the main folds of the G-quadruplex structures. Notably, a binding preference was found for both ligands towards the hybrid telomeric G-quadruplex. Moreover, compounds <b>3</b> and <b>6</b> proved to be active on different human cancer cells in the low micromolar range. Overall, these compounds emerged as useful ligands able to target G-quadruplex structures, which are of interest as promising starting scaffolds for the design of analogues endowed with high and selective anticancer activity.https://www.mdpi.com/1422-0067/24/9/7765G-quadruplexnatural compoundscancerdihydrophenanthrenoidsglucosides |
| spellingShingle | Chiara Platella Andrea Criscuolo Claudia Riccardi Rosa Gaglione Angela Arciello Domenica Musumeci Marina DellaGreca Daniela Montesarchio Exploring the Binding of Natural Compounds to Cancer-Related G-Quadruplex Structures: From 9,10-Dihydrophenanthrenes to Their Dimeric and Glucoside Derivatives International Journal of Molecular Sciences G-quadruplex natural compounds cancer dihydrophenanthrenoids glucosides |
| title | Exploring the Binding of Natural Compounds to Cancer-Related G-Quadruplex Structures: From 9,10-Dihydrophenanthrenes to Their Dimeric and Glucoside Derivatives |
| title_full | Exploring the Binding of Natural Compounds to Cancer-Related G-Quadruplex Structures: From 9,10-Dihydrophenanthrenes to Their Dimeric and Glucoside Derivatives |
| title_fullStr | Exploring the Binding of Natural Compounds to Cancer-Related G-Quadruplex Structures: From 9,10-Dihydrophenanthrenes to Their Dimeric and Glucoside Derivatives |
| title_full_unstemmed | Exploring the Binding of Natural Compounds to Cancer-Related G-Quadruplex Structures: From 9,10-Dihydrophenanthrenes to Their Dimeric and Glucoside Derivatives |
| title_short | Exploring the Binding of Natural Compounds to Cancer-Related G-Quadruplex Structures: From 9,10-Dihydrophenanthrenes to Their Dimeric and Glucoside Derivatives |
| title_sort | exploring the binding of natural compounds to cancer related g quadruplex structures from 9 10 dihydrophenanthrenes to their dimeric and glucoside derivatives |
| topic | G-quadruplex natural compounds cancer dihydrophenanthrenoids glucosides |
| url | https://www.mdpi.com/1422-0067/24/9/7765 |
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